RELATED APPLICATION S

[0001] The present application claims priority to U.S. Provisional Application Serial No. 62/288,316, entitled "Chimeric Hepatitis D Virus Antigen And Hepatitis B Virus PRE S I Genes For Use Alone Or In Vaccines Containing Hepatitis B Virus Genes" filed January 28, 2016, the contents of which are hereby expressly incorporated by reference in their entirety.

REFERENCE TO SEQUENCE LISTING, TABLE, O COMPUTER PROGRAM

LISTING

[0002] The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled SEQLISTSVF002WO.TXT created January 25, 2017, which is 233 kb in size. The information is the electronic format of the Sequence Listing is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

[0003] Described herein are chimeric genes that overcome genotype variability. Hepatitis D virus (HDV) genotype 1 sequences, which serve as an adjuvant in patients infected by genotype 2 HDV strains, are utilized. Moreover, the HDV genes are linked to a sequence encoding a part of the PreS l region of the Hepatitis B vims (HBV). By this approach, neutralizing antibodies and T cells to HBV and HDV are generated. These can be used alone or be combined with genes or proteins expressing HBV proteins to raise both HBV and HDV specific immune responses in patients with HBV. These constructs are used as both genetic and protein-based vaccines or immunogenic compositions, which inhibit, ameliorate, treat and/or prevent HDV and/or HBV infections. BAC KGROUN D

[0004] Hepatitis is a disease resulting in swelling and inflammation of the liver. This disorder is commonly caused by viruses, five types of which are currently known (Hepatitis A, B, C, D and E). The hepatitis D virus (HDV) causes severe liver disease and cancer in patients infected by the hepatitis B vims (HBV). HDV exist in three major genotypes world-wide. Hepatitis D virus (HDV), also referred to as Hepatitis delta vims, is a small, spherical single-stranded circular RNA virus. The entire virus was cloned and sequenced in 1986, and given the genus of Deltavirus. HDV is structurally unrelated to the other hepatitis viruses. Since HDV is an incomplete virus, it can only replicate in the presence of Hepatitis B (HBV) vims, which provides structural components for HDV. Ei particular, HDV has an outer coat that contains large, medium and small hepatitis B surface antigens, and host lipids surrounding an inner nucleocapsid, which contains about 200 molecules of hepatitis D antigen (HDAg) for each genome. The circular genome of HDV is unique to animal viruses because of its high GC content.

[0005] HDV produces a single protein, namely hepatitis D antigen (HDAg). HDAg exists in two isoforms: a 27kDa large-HDAg (HDAg-L), and a 24 kDa small- HDAg (HDAg-S). The two sequences differ in that the C-terminus of the HDAg-L contains an additional 19 amino acids not found in HDAg-S, which are essential to vims assembly. Both isoforms are produced from the same open reading frame (ORF), which contains a UAG stop codon at codon 196, which normally produces only the HDAg-S. However, editing by the cellular enzyme adenosine deaminase- 1 changes the stop codon to UCG, allowing HDAg-L to be produced, HDAg-S is produced in the early stages of infection, enters the nucleus and supports viral replication. In contrast, HDAg-L is produced during the later stages of infection, acts as an inhibitor of viral replication, and is required for assembly of viral particles. Both isoforms bind RNA, with a specificity for the rod-like folding of the HDV genome and antigenome (Chao et ai., J Virol, 65:4057- 4062, 1991; Lee et al, J. Virol, 67:2221-2227, 1993). HDAg contains a coiied-coil dimerization domain, nuclear localization signal, RNA-binding domain, and a putative assembly domain. Various epitopes of HDAg were determined to be exposed by PEPSCAN, immunoprecipitation analysis and ELISA, including those within amino acids 12-60, 58-78, 82-102, 123-143, 156-184, 167-184 and 197-211 (Bichko et al., (1996) J. Virol 70:5807-581 1). Epitope mapping of HDAg in patients with chronic Hepatitis D

9 infection exhibited the following potential cytotoxic T-ligand epitopes: amino acids 43 to 51 , 50 to 58 and 1 14 to 122 (Wang et al„ J. Virol, 81 :4438-4444, 2007).

[0006] HDV is transmitted through percutaneous or mucosal contact with infected blood. HDV can be acquired by either simultaneous infection with HBV (coinfection), or by superinfection, in, which HDV is superimposed on chronic HBV infection or carrier state. Both types of infection result in more deleterious effects than infection solely with HBV, including enhanced possibility of liver failure and more rapid onset of cirrhosis and potentially liver cancer. The combination of HBV and HDV results in the highest mortality rate of all hepatitis infections at about 20%. There is no current vaccine for HDV, but it can be prevented in individuals who are not already infected with HBV by HBV vaccination.

[0007] HDV is structurally unrelated to the other hepatitis viruses. As HDV is an incomplete virus, it can only replicate in the presence of Hepatitis B (HBV) virus, which provides structural components for HDV, HDV is a defect virus, or a viroid, that lacks the ability to productively infect a liver cell on its own. In particular, HDV has an outer coat that contains large, medium and small hepatitis B surface antigens, and host lipids surrounding an inner nucleocapsid, which contains about 200 molecules of hepatitis D antigen (HDAg) for each genome. The circular genome of HDV is unique to animal viruses because of its high GC content. The 1700 base circular positive RNA genome encodes a single protein, the small (S) hepatitis D antigen (S-HDAg) that acts as the viral capsid. However, a posttranscriptional editing of the S-HDAg stop codon in the transcribed genome results in the production of a 19 amino acid longer large (L-HDAg), which acts as a regulator of transcription. The replication of the viral RNA genome takes place in the nucleus through a rolling circle mechanism using host cell RNA polymerases. The use of host RNA polymerase for genome synthesis makes it extremely difficult to develop non-toxic antiviral polymerase inhibitors. The roiling circle replication results in a more than full length genomic RNA than is trimmed to the genomic RNA by hammerhead ribozymes and then circularized. For assembly and release of viral particles HDV will steal the surface protein of HBV, HBsAg, Thus, the HDV virion leaving the cell is encompassed of HDAg enclosing the viral RNA genome with a lipid envelope containing HBsAg.

[0008] Since all cells infected by HBV express and secrete high levels of HBsAg particles, and importantly, HBsAg expression can be completely independent of the HBV replication, this means that HDV uses the same entry receptor as HBV, the sodium taurocholate co-transporting polypeptide (NTCP) and can only productively infect cells infected by HBV.

[0009] HDV can be prevented by HBV vaccination in a host naive to both HBV and HDV. However, since the HBV vaccine is based on HBsAg this vaccine is useless in a person already infected with HBV. Thus, there is no strategy currently to prevent HDV infection in HBV carriers. In addition, since the production of HBsAg is independent of the HBV replication, the currently used polymerase inhibitors for HBV cannot be used to prevent or to treat the HDV coinfection.

[0010] Potent antiviral drugs inhibit HBV replication without affecting the HD V replication. Thus antiviral drugs affect neither the production of the HB V envelope (HBsAg) required for HDV assembly, nor the replication of the HDV genome mediated by the host cell RNA polymerase II. The latter significantly impairs the possibility to develop antiviral enzyme inhibitors for HDV, HBsAg-based HBV vaccines can prevent a non-infected subject from becoming infected by both HBV and HDV; however, the HBV vaccine cannot protect a subject already infected by HBV against HDV super-infection due to the inherent overproduction of HBsAg during the HBV infection. HDV RNA replication is mediated by host cell RNA polymerase II, which significantly impairs the possibility to develop antiviral enzyme inhibitors. The HBV infection can be treated with a life-long therapy using polymerase inhibitors that blocks HBV replication, but not protein synthesis, and reduces the risk of HBV-induced liver damage. However, HDV replication is completely unaffected by the HBV antivirals since these do not block HBsAg production. The only treatment available for HDV today is an expensive and cumbersome 48-month therapy of pegylated interferon (PEG-IFN), which cures 25% of HDV infections. Thus, new preventive and therapeutic strategies are desperately needed for the increasing problem of HBV-HDV coinfections.

SUMMARY OF THE INVENTION

[0011] In a first aspect, a chimeric gene comprising HDAg sequences is provided. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preSl derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HDAg genotype 1 B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine tesehovirus-1 2 A (P2A), foot-and-mouth disease vims (FMDV) 2A (F2A), equine rhinitis A virus (ERAV) 2A (E2A) and Thosea asigna virus 2A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine- serine-glycine) motif at an N-terminus. In some alternatives, the at least one preSl derived sequence is preSl A and/or preSl B. In some alternatives, the at least one pre SI derived sequence is preSl A and comprises an amino acid sequence set forth in SEQ ID NO: 1 . In some alternatives, the at least one preSl derived sequence is pre SI B and comprises an amino acid sequence set forth in SEQ ID NO: 2. In some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4. In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, preSl B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. in some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding HD Ag genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least- two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 10 or 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 15 or 17. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 20 or 22. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 25 or 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's: 30 or 32, In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 35 or 37. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 40 or 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ) ID NO:'s 45 or 47. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50 or 52. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 55 or 57. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59, In some alternatives, the chimeric gene further comprises sequences encoding HBV Core or an antigenic or immunogenic portion thereof (e.g., a portion that improves an immunological response to a co-administered nucleic acid, such as a portion that promotes an adjuvant activity with respect to a coadministered nucleic acid). In some alternatives, the HBV Core or an antigenic or immunogenic portion thereof is a human HBV Core or an antigenic or immunogenic portion thereof, a rodent HB V Core or an antigenic or immunogenic portion thereof, such as a woodchuck or ground squirrel HBV Core or antigenic or immunogenic portion thereof, or an avian HBV Core or an antigenic or immunogenic portion thereof, such as a stork or heron HBV Core or an immunogenic portion thereof. In some alternatives, the sequences encoding the HBV Core or antigenic portion thereof comprises a sequence set forth in SEQ ID NO: 60 or 62 or an antigenic portion thereof.

[0012] In some alternatives, the HBV Core or antigenic portion thereof comprises an amino acid sequence set forth in SEQ ID NO: 64 or an antigenic portion thereof. In some alternatives, the chimeric gene further comprises sequences encoding Pre-C-gt-H. In some alternatives, the sequences encoding the Pre-C-gt-H comprise a sequence set forth in SEQ ID NO: 65 or 67. In some alternatives, the Pre-C-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 69. in some alternatives, the chimeric gene further comprises sequences encoding PreC-C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt-H comprise a sequence set forth in SEQ ID NO: 70 or 72. In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 74. In some alternatives, the chimeric gene is codon optimized for expression in humans.

[0013] In a second aspect, a chimeric protein comprising at least two HDAg protein domains, encoded by the chimeric gene of anyone of the alternatives described herein is provided. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preS l derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HDAg genotype 1 B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2A (P2A), foot-and-mouth disease virus (FMDV) 2A (F2A), equine rhinitis A virus (ERAV) 2 A (E2A) and Thosea asigna virus 2 A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine-serine-glycine) motif at an N-terminus. In some alternatives, the at least one preSl derived sequence is preSl A and/or preSl B. In some alternatives, the at least one preSl derived sequence is preSl A and comprises an amino acid sequence set forth in SEQ ID NO: 1. In some alternatives, the at least one preSl derived sequence is preSl B and comprises an amino acid sequence set forth in SEQ ID NO: 2. In some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4. In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, preSl B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 10 or 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 15 or 17. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 20 or 22. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24. in some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 25 or 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's: 30 or 32. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 35 or 37, In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 40 or 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 45 or 47. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50 or 52. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 55 or 57, In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59 In some alternatives, the chimeric gene further comprises sequences encoding HBV Core or an antigenic or immunogenic portion thereof (e.g., a portion that improves an immunological response to a co-administered nucleic acid, such as a portion that promotes an adjuvant activity with respect to a coadministered nucleic acid). In some alternatives, the HBV Core or an antigenic or immunogenic portion thereof is a human HBV Core or an antigenic or immunogenic portion thereof, a rodent HBV Core or an antigenic or immunogenic portion thereof such as a woodchuck or ground squirrel HBV Core or antigenic or immunogenic portion thereof, or an avian HBV Core or an antigenic or immunogenic portion thereof, such as a stork or heron HBV Core or an immunogenic portion thereof. In some alternatives, the sequences encoding the HBV Core or antigenic portion thereof comprises a sequence set forth in SEQ ID NO: 60 or 62 or an antigenic portion thereof. In some alternatives, the HBV Core or antigenic portion thereof comprises an amino acid sequence set forth in SEQ ID NO: 64 or an antigenic portion thereof. In some alternatives, the chimeric gene further comprises sequences encoding Pre-C-gt-H. In some alternatives, the sequences encoding the Pre-C-gt-H comprise a sequence set forth in SEQ ID NO: 65 or 67. In some alternatives, the Pre-C-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 69. In some alternatives, the chimeric gene further comprises sequences encoding PreC- C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt-H comprise a sequence set forth in SEQ ID NO: 70 or 72. In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 74, In some alternatives, the chimeric gene is codon optimized for expression in humans.

[0014] In a third aspect, a composition comprising anyone or more of the chimeric genes of any one of the alternatives is provided. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preSl derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HDAg genotype 1 B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2A (P2A), foot-and-mouth disease virus (FMDV) 2A (F2A), equine rhinitis A virus (ERAV) 2A (E2A) and Thosea asigna virus 2 A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine- serine-glycine) motif at an N-terminus. In some alternatives, the at least one preSl derived sequence is preS l A and/or preS l B. In some alternatives, the at least one preSl derived sequence is preS l A and comprises an amino acid sequence set forth in SEQ ID NO: 1. In some alternatives, the at least one preSl derived sequence is preSl B and comprises an amino acid sequence set forth in SEQ ID NO: 2. In some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4. In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, preSl B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO; 7, In some alternatives, the at least two sequences comprises a sequence encoding HD Ag genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 10 or 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 15 or 17. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 20 or 22. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NQ:'s 25 or 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's; 30 or 32. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 35 or 37. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 40 or 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 45 or 47. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50 or 52. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 55 or 57. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59, In some alternatives, the chimeric gene further comprises sequences encoding HBV Core or an antigenic or immunogenic portion thereof (e.g., a portion that improves an immunological response to a co-administered nucleic acid, such as a portion that promotes an adjuvant activity with respect to a co-administered nucleic acid). In some alternatives, the HBV Core or an antigenic or immunogenic portion thereof is a human HBV Core or an antigenic or immunogenic portion thereof, a rodent HBV Core or an antigenic or immunogenic portion thereof, such as a woodchuck or ground squirrel HBV Core or antigenic or immunogenic portion thereof, or an avian HBV Core or an antigenic or immunogenic portion thereof, such as a stork or heron HBV Core or an immunogenic portion thereof. In some alternatives, the sequences encoding the HBV Core or antigenic portion thereof comprises a sequence set forth in SEQ ID NO: 60 or 62 or an antigenic portion thereof. In some alternatives, the HBV Core or antigenic portion thereof comprises an amino acid sequence set forth in SEQ ID NO: 64 or an antigenic portion thereof. In some alternatives, the chimeric gene further comprises sequences encoding Pre-C-gt-H. In some alternatives, the sequences encoding the Pre-C-gt-H comprise a sequence set forth in SEQ ID NO: 65 or 67. In some alternatives, the Pre-C-gt- H comprises an amino acid sequence set forth in SEQ ID NO: 69. In some alternatives, the chimeric gene further comprises sequences encoding PreC-C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt-H comprise a sequence set forth in SEQ ID NO: 70 or 72. In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 74. In some alternatives, the chimeric gene is codon optimized for expression in humans. In some alternatives, the composition further comprises the chimeric protein of anyone of the alternatives herein. In some alternatives, the chimeric protein is encoded by any one of the chimeric genes provided herein. In some alternatives, the composition further comprises an adjuvant. In some alternatives, said adjuvant comprises a nucleic acid encoding a polypeptide adjuvant. In some alternatives, said polypeptide adjuvant is IL-12, IL-15, or IL-21. In some alternatives, said adjuvant is ribavirin or a CpG-containing nucleic acid. In some alternatives, said adjuvant is a polypeptide. In some alternatives, said adjuvant comprises an adjuvant promoting portion or subunit of IL-12, IL-15, or IL-21.

[0015] In a fourth aspect, the chimeric gene or composition of any one of the alternatives is for use in generating an immune response in a subject or for DNA vaccination so as to inhibit, ameliorate, treat, or prevent HBV and HDV infection. In some alternatives, the composition comprises anyone or more of the chimeric genes of any one of the alternatives described herein. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preSl derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HDAg genotype 1 B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2 A (P2A), foot-and-mouth disease virus (FMDV) 2A (F2A), equine rhinitis A vims (ERAV) 2A (E2A) and Thosea asigna virus 2A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine- serine-glycine) motif at an N-terminus. In some alternatives, the at least one preSl derived sequence is preSl A and/or preSl B. In some alternatives, the at least one preSl derived sequence is preSl A and comprises an amino acid sequence set forth in SEQ ID NO: 1. In some alternatives, the at least one preS l derived sequence is preSl B and comprises an amino acid sequence set forth in SEQ ID NO: 2. In some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4. In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, pre SI B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO; 8, In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO' s 10 or 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO' s 15 or 1 7. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO; 19. In some alternatives, the chimeric gene compri ses a nucleic acid sequence set forth in SEQ ID NO' s 20 or 22, In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: ' s 25 or 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO' s: 30 or 32. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: ' s 35 or 37. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: ' s 40 or 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44. In some alternatives, the chimeric gene compri ses a nucleic acid sequence set forth in SEQ ID NO: ' s 45 or 47. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49. In some alternatives, the chimeric gene compri ses a nucleic acid sequence set forth in SEQ ID NO: 50 or 52. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 's 55 or 57. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59. In some alternatives, the chimeric gene further comprises sequences encoding HBV Core or an antigenic or immunogenic portion thereof (e.g., a portion that improves an immunological response to a co-administered nucleic acid, such as a portion that promotes an adjuvant activity with respect to a co-administered nucleic acid). In some alternatives, the HBV Core or an antigenic or immunogenic portion thereof is a human HBV Core or an antigenic or immunogenic portion thereof, a rodent HBV Core or an antigenic or immunogenic portion thereof, such as a woodchuck or ground squirrel HBV Core or antigenic or immunogenic portion thereof, or an avian HBV Core or an antigenic or immunogenic portion thereof, such as a stork or heron HBV Core or an immunogenic portion thereof. In some alternatives, the sequences encoding the HBV Core or antigenic portion thereof comprises a sequence set forth in SEQ ID NO: 60 or 62 or an antigenic portion thereof. In some alternatives, the HBV Core or antigenic portion thereof comprises an amino acid sequence set forth in SEQ ID NO: 64 or an antigenic portion thereof. In some alternatives, the chimeric gene further comprises sequences encoding Pre-C-gt-H. In some alternatives, the sequences encoding the Pre-C-gt-H comprise a sequence set forth in SEQ ID NO: 65 or 67. In some alternatives, the Pre-C-gt- H comprises an amino acid sequence set forth in SEQ ID NO: 69. In some alternatives, the chimeric gene further comprises sequences encoding PreC-C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt-H comprise a sequence set forth in SEQ ID NO: 70 or 72. In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 74. In some alternatives, the chimeric gene is codon optimized for expression in humans. In some alternatives, the composition further comprises the chimeric protein of anyone of the alternatives herein. In some alternatives, the chimeric protein is encoded by any one of the chimeric genes provided herein. In some alternatives, the composition further comprises an adjuvant. In some alternatives, said adjuvant comprises a nucleic acid encoding a polypeptide adjuvant. In some alternatives, said polypeptide adjuvant is IL-12, IL-15, or IL-21. In some alternatives, said adjuvant is ribavirin or a CpG-containing nucleic acid. In some alternatives, said adjuvant is a polypeptide. In some alternatives, said adjuvant comprises an adjuvant promoting portion or subunit of IL-12, IL-15, or IL-21.

[0016] In a fifth aspect, the chimeric gene or composition of any one of the alternatives herein, is for use in generating an antibody, T-lymphocyte or CTL-specific response in a subject so as to inhibit, ameliorate, treat, or prevent an HBV and HDV infection. In some alternatives, the composition comprises anyone or more of the chimeric genes of any one of the alternatives described herein. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one pre SI derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HDAg genotype 1 B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2A (P2A), foot-and-mouth disease virus (FMDV) 2A (F2A), equine rhinitis A virus (ERAV) 2A (E2A) and Thosea asigna virus 2A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine- serine-glycine) motif at an N-temiinus. In some alternatives, the at least one preSl derived sequence is preSl A and/or preSl B. In some alternatives, the at least one preS l derived sequence is preSl A and comprises an amino acid sequence set forth in SEQ ID NO: 1. In some alternatives, the at least one preSl derived sequence is preSl B and comprises an amino acid sequence set forth in SEQ ID NO: 2. In some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4. In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, preSl B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene compri ses a nucleic acid sequence set forth in SEQ ID NO's 10 or 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 15 or 17. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 20 or 22, In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 25 or 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's: 30 or 32. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 35 or 37. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 40 or 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 45 or 47. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50 or 52, In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 55 or 57. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59. In some alternatives, the chimeric gene further comprises sequences encoding HBV Core or an antigenic or immunogenic portion thereof (e.g., a portion that improves an immunological response to a co-administered nucleic acid, such as a portion that promotes an adjuvant activity with respect to a co-administered nucleic acid). In some alternatives, the HBV Core or an antigenic or immunogenic portion thereof is a human HBV Core or an antigenic or immunogenic portion thereof, a rodent HBV Core or an antigenic or immunogenic portion thereof, such as a woodchuck or ground squirrel HBV Core or antigenic or immunogenic portion thereof, or an avian HBV Core or an antigenic or immunogenic portion thereof, such as a stork or heron HBV Core or an immunogenic portion thereof. In some alternatives, the sequences encoding the HBV Core or antigenic portion thereof comprises a sequence set forth in SEQ ID NO: 60 or 62 or an antigenic portion thereof. In some alternatives, the HBV Core or antigenic portion thereof comprises an amino acid sequence set forth in SEQ ID NO: 64 or an antigenic portion thereof. In some alternatives, the chimeric gene further comprises sequences encoding Pre-C-gt-H. In some alternatives, the sequences encoding the Pre-C-gt-H comprise a sequence set forth in SEQ ID NO: 65 or 67. In some alternatives, the Pre-C-gt- H comprises an amino acid sequence set forth in SEQ ID NO: 69. In some alternatives, the chimeric gene further comprises sequences encoding PreC-C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt-H comprise a sequence set forth in SEQ ID NO: 70 or 72, In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 74. In some alternatives, the chimeric gene is codon optimized for expression in humans. In some alternatives, the composition further comprises the chimeric protein of anyone of the alternatives herein. In some alternatives, the chimeric protein is encoded by any one of the chimeric genes provided herein. In some alternatives, the composition further comprises an adjuvant. In some alternatives, said adjuvant comprises a nucleic acid encoding a polypeptide adjuvant. In some alternatives, said polypeptide adjuvant is IL-12, IL-15, or IL-21 . In some alternatives, said adjuvant is ribavirin or a CpG-containing nucleic acid. In some alternatives, said adjuvant is a polypeptide. In some alternatives, said adjuvant comprises an adjuvant promoting portion or subunit of IL- 12, IL- 15, or IL-21.

[0017] In a sixth aspect, the chimeric gene or composition of any one of the alternatives described herein is for DNA vaccination against HBV and HDV in a subject that has been identified as having and HDV or HBV infection. In some alternatives, the composition comprises anyone or more of the chimeric genes of any one of the alternatives described herein. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preSl derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype I A, HDAg genotype 1 B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2A (P2A), foot-and-mouth disease virus (FMDV) 2A (F2A), equine rhinitis A virus (ERAV) 2A (E2A) and Thosea asigna virus 2A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine-serine-glycine) motif at an N-terminus. In some alternatives, the at least one preSl derived sequence is preSl A and/or pre SI B. In some alternatives, the at least one preS l derived sequence is preS l A and comprises an amino acid sequence set forth in SEQ ID NO: 1. In some alternatives, the at least one preSl derived sequence is preSl B and comprises an amino acid sequence set forth in SEQ ID NO: 2. In some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ) ID NO: 4, In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, pre SI B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ) ID NO's 10 or 12, In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 15 or 17. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 20 or 22. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 25 or 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's: 30 or 32. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 35 or 37. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID O:'s 40 or 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 45 or 47. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50 or 52. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 55 or 57. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59. In some alternatives, the chimeric gene further comprises sequences encoding HBV Core or an antigenic or immunogenic portion thereof (e.g., a portion that improves an immunological response to a co-administered nucleic acid, such as a portion that promotes an adjuvant activity with respect to a coadministered nucleic acid). In some alternatives, the HBV Core or an antigenic or immunogenic portion thereof is a human HBV Core or an antigenic or immunogenic portion thereof, a rodent HBV Core or an antigenic or immunogenic portion thereof such as a woodchuck or ground squirrel HBV Core or antigenic or immunogenic portion thereof, or an avian HBV Core or an antigenic or immunogenic portion thereof, such as a stork or heron HBV Core or an immunogenic portion thereof. In some alternatives, the sequences encoding the HBV Core or antigenic portion thereof comprises a sequence set forth in SEQ ID NO: 60 or 62 or an antigenic portion thereof. In some alternatives, the HBV Core or antigenic portion thereof comprises an amino acid sequence set forth in SEQ ID NO: 64 or an antigenic portion thereof. In some alternatives, the chimeric gene further comprises sequences encoding Pre-C-gt-H. In some alternatives, the sequences encoding the Pre-C-gt-H comprise a sequence set forth in SEQ ID NO: 65 or 67. In some alternatives, the Pre-C-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 69. In some alternatives, the chimeric gene further comprises sequences encoding PreC- C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt-H comprise a sequence set forth in SEQ ID NO: 70 or 72. In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 74. In some alternatives, the chimeric gene is codon optimized for expression in humans. In some alternatives, the composition further comprises the chimeric protein of anyone of the alternatives herein. In some alternatives, the chimeric protein is encoded by any one of the chimeric genes provided herein. In some alternatives, the composition further comprises an adjuvant. In some alternatives, said adjuvant comprises a nucleic acid encoding a polypeptide adjuvant. In some alternatives, said polypeptide adjuvant is IL-12, IL-15, or IL-21. In some alternatives, said adjuvant is ribavirin or a CpG-containing nucleic acid. In some alternatives, said adjuvant is a polypeptide. In some alternatives, said adjuvant comprises an adjuvant promoting portion or subunit of IL- 12, IL-15, or IL-21.

[0018] In a seventh aspect, a method of eliciting an immune response is provided, wherein the method comprises administering to a subject having HDV infection and/or HBV infection the nucleic acid or composition of any one of the alternatives herein. In some alternatives, the composition comprises anyone or more of the chimeric genes of any one of the alternatives described herein. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one pre SI derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HDAg genotype I B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-l 2A (P2A), foot-and-mouth disease virus (FMDV) 2A (F2A), equine rhinitis A virus (ERAV) 2A (E2A) and Thosea asigna virus 2A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine- serine-glycine) motif at an N-terminus. In some alternatives, the at least one preSl derived sequence is preSl A and/or preS l B. In some alternatives, the at least one preSl derived sequence is preSl A and comprises an amino acid sequence set forth in SEQ ID NO: 1. In some alternatives, the at least one preSl derived sequence is preSl B and comprises an amino acid sequence set forth in SEQ ID NO: 2. In some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4. In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, pre SI B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding IIDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8, In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 10 or 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 15 or 17. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 20 or 22. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 25 or 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's: 30 or 32. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 35 or 37. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NQ:'s 40 or 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 45 or 47. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50 or 52. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 55 or 57, In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59. In some alternatives, the chimeric gene further comprises sequences encoding HBV Core or an antigenic or immunogenic portion thereof (e.g., a portion that improves an immunological response to a co-administered nucleic acid, such as a portion that promotes an adjuvant activity with respect to a co-administered nucleic acid). In some alternatives, the HBV Core or an antigenic or immunogenic portion thereof is a human HBV Core or an antigenic or immunogenic portion thereof, a rodent HBV Core or an antigenic or immunogenic portion thereof, such as a woodchuck or ground squirrel HBV Core or antigenic or immunogenic portion thereof, or an avian HBV Core or an antigenic or immunogenic portion thereof, such as a stork or heron HBV Core or an immunogenic portion thereof. In some alternatives, the sequences encoding the HBV Core or an antigenic portion thereof comprises a sequence set forth in SEQ ID NO: 60 or 62 or an antigenic portion thereof. In some alternatives, the HBV Core or antigenic portion thereof comprises an amino acid sequence set forth in SEQ ID NO: 64 or an antigenic portion thereof. In some alternatives, the chimeric gene further comprises sequences encoding Pre-C-gt-H. In some alternatives, the sequences encoding the Pre-C- gt-H comprise a sequence set forth in SEQ ID NO: 65 or 67, In some alternatives, the Pre- C-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 69, In some alternatives, the chimeric gene further comprises sequences encoding PreC-C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt-H comprise a sequence set forth in SEQ ID NO: 70 or 72. In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 74. In some aiteraatives, the chimeric gene is codon optimized for expression in humans. In some alternatives, the composition further comprises the chimeric protein of anyone of the alternatives herein. In some alternatives, the chimeric protein is encoded by any one of the chimeric genes provided herein. In some alternatives, the composition further comprises an adjuvant. In some alternatives, said adjuvant comprises a nucleic acid encoding a polypeptide adjuvant. In some aiteraatives, said polypeptide adjuvant is IL-12, IL-15, or IL-2I , In some alternatives, said adjuvant is ribavirin or a CpG-containing nucleic acid. In some alternatives, said adjuvant is a polypeptide. In some aiteraatives, said adjuvant comprises an adjuvant promoting portion or subunit of IL-12, IL-15, or IL-21. In some alternatives, said administering comprises injecting said nucleic acid into a patient, such as using an rVIN needle with or without electroporation. In some alternatives, the method further Δ- comprising administering a second administration of a nucleic acid or composition of any one of the alternatives described herein. In some alternatives, the method further comprises providing an adjuvant. In some alternatives, said adjuvant is a nucleic acid encoding a polypeptide adjuvant, such as IL-12, IL-15, or IL-21. In some alternatives, said adjuvant is IL-12, IL-15, or IL-21. In some alternatives, said second administration is given after said first time. In some alternatives, said adjuvant is given before, during, or after administration of said nucleic acid or composition of any one of claims 1-45. In some alternatives, said second administration is given one week, two weeks, three weeks, four weeks, five weeks, or six weeks after the first administration of said nucleic acid or composition of any one of claims 1-45. In some alternatives, the subject has been identified as a person at risk of contracting HDV or that has HDV. In some alternatives, the method further comprises evaluating the subject for an immunoresponse after administering the compositions of anyone of the alternatives here. In some alternatives, the evaluating is performed by an ELISpot assay. In some alternatives, the ELISpot assay is performed using any one of the peptides comprising a sequence set forth in SEQ ID NO: 75-116.

[0019] In an eighth aspect, a method of increasing preSl antibodies in a subject in need, the method comprising administering the compositions of anyone of the alternatives described herein to the subject in need. In some alternatives, the composition comprises anyone or more of the chimeric genes of any one of the alternatives described herein. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preSl derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HDAg genotype 1 B, HD Ag genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2A (P2A), foot-and-mouth disease virus (FMDV) 2A (F2A), equine rhinitis A virus (ERAV) 2A (E2A) and Thosea asigna virus 2A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine-serine-glycine) motif at an N-terminus. In some alternatives, the at least one preSl derived sequence is preSl A and/or pre SI B. In some alternatives, the at least one pre SI derived sequence is preSl A and comprises an amino acid sequence set forth in SEQ ID NO: 1. In some alternatives, the at least one preSl derived sequence is preSl B and comprises an amino acid sequence set forth in SEQ ID NO: 2. In some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4. In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, preSl B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 10 or 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 15 or 17, In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ED NO's 20 or 22. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 25 or 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ) ID NO's: 30 or 32, In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 35 or 37. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 40 or 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID O:'s 45 or 47, In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50 or 52. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 55 or 57. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59. In some alternatives, the chimeric gene further comprises sequences encoding HBV Core or an antigenic or immunogenic portion thereof (e.g., a portion that improves an immunological response to a co-administered nucleic acid, such as a portion that promotes an adjuvant activity with respect to a coadministered nucleic acid). In some alternatives, the HBV Core or an antigenic or immunogenic portion thereof is a human HBV Core or an antigenic or immunogenic portion thereof, a rodent HBV Core or an antigenic or immunogenic portion thereof, such as a woodchuck or ground squirrel HBV Core or antigenic or immunogenic portion thereof, or an avian HBV Core or an antigenic or immunogenic portion thereof, such as a stork or heron HBV Core or an immunogenic portion thereof. In some alternatives, the sequences encoding the HBV Core or antigenic portion thereof comprises a sequence set forth in SEQ ID NO: 60 or 62 or an antigenic portion thereof. In some alternatives, the HBV Core comprises an amino acid sequence set forth in SEQ ID NO: 64 or an antigenic portion thereof. In some alternatives, the chimeric gene further comprises sequences encoding Pre-C-gt-H. In some alternatives, the sequences encoding the Pre-C-gt-H comprise a sequence set forth in SEQ ID NO: 65 or 67. In some alternatives, the Pre-C-gt- H comprises an amino acid sequence set forth in SEQ ID NO: 69. In some alternatives, the chimeric gene further comprises sequences encoding PreC-C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt-H comprise a sequence set forth in SEQ ID NO: 70 or 72. In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 74. In some alternatives, the chimeric gene is codon optimized for expression in humans. In some alternatives, the composition further comprises the chimeric protein of anyone of the alternatives herein. In some alternatives, the chimeric protein is encoded by any one of the chimeric genes provided herein. In some alternatives, the composition further comprises an adjuvant. In some alternatives, said adjuvant comprises a nucleic acid encoding a polypeptide adjuvant. In some alternatives, said polypeptide adjuvant is IL-12, IL-15, or IL-21. In some alternatives, said adjuvant is ribavirin or a CpG-containing nucleic acid. In some alternatives, said adjuvant is a polypeptide. In some alternatives, said adjuvant comprises an adjuvant promoting portion or subunit of IL-12, IL-15, or IL-21. In some alternatives, the method further comprises evaluating the subject for an immunoresponse after administering the compositions of anyone of the alternatives here. In some alternatives, the evaluating is performed by an ELISpot assay. In some alternatives, the ELISpot assay is performed using any one of the peptides comprising a sequence set forth in SEQ ID NO: 75-116.

BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 shows the alignment of HBV preS l peptides.

[0021] Figure 2 is a schematic of several primary sequences of combined HDV-PreSl vaccine design. As shown, the HDV-PreSl 's can have domains from HDAg genotype I A/B, PreSl A/B, P2A and HDAg gt2 A/B to make up the vaccines Delta- 1, Delta-2, Delta-3, Delta-4, Delta-5, Delta-6, Delta-7, Delta-8, Delta-9 and Delta 10.

[0022] Figure 3 shows the primary structures of the HBv-PreC/C vaccine designs, Core-1, Core-2 and Core-3.

[0023] Figure 4A-4T shows an in vitro recall of T cells primed after a single immunization using HDV constructs 1-10 towards gtl (right panel) or gt:2 (left panel) peptides (Peptides are shown in Table 1). The peptide constructs are also shown above the graphs.

[0024] Figure 5A-5T shows an in vitro recall of T cells primed after two monthly immunizations using HDV constructs 1 -10 towards gtl (right panel) or gt2 (left panel) peptides (Peptides are shown in Table 1).

[0025] Figure 6 A and 6B show the in vitro expression analysis of the 10 HDV constructs. In brief, cells were transfected with the respective plasmid, cells were lysed and run on an denaturating SDS-PAGE gel, transferred to a nitrocellulose filter, and blotted with either a preSl -specific antibody (6A) of a HDAg-specific antibody or an anti- HDV antibody (613). Definitions

[0026] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains.

[0Θ27] "About" as used herein when referring to a measurable value is meant to encompass variations of ±20% or ±10%, more preferably ±5%, even more preferably ±1%, and still more preferably ±0.1 % from the specified value.

[0028] As used herein, "nucleic acid" or "nucleic acid molecule" refers to polynucleotides, such as deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), oligonucleotides, fragments generated by the polymerase chain reaction (PCR), and fragments generated by any of ligation, scission, endonuclease action, and exonuclease action. Nucleic acid molecules can be composed of monomers that are naturally-occurring nucleotides (such as DNA and RNA), or analogs of naturally-occurring nucleotides (e.g., enantiomeric forms of naturally-occurring nucleotides), or a combination of both. Modified nucleotides can have alterations in sugar moieties and/or in pyrimidine or purine base moieties. Sugar modifications include, for example, replacement of one or more hydroxyl groups with halogens, alkyl groups, amines, and azido groups, or sugars can be functionalized as ethers or esters. Moreover, the entire sugar moiety can be replaced with sterically and electronically similar structures, such as aza-sugars and carbocyclic sugar analogs. Examples of modifications in a base moiety include alkylated purines and pyrimidines, acylated purines or pyrimidines, or other well-known heterocyclic substitutes. Nucleic acid monomers can be linked by phosphodiester bonds or analogs of such linkages. Analogs of phosphodiester linkages include phosphorothioate, phosphorodithioate, phosphoroseienoate, phosphorodiselenoate, phosphoroanilothioate, phosphoranilidate, or phosphoramidate. The term "nucleic acid molecule" also includes so-called "peptide nucleic acids," which comprise naturally-occurring or modified nucleic acid bases attached to a polyamide backbone. Nucleic acids can be either single stranded or double stranded. In some alternatives described herein, a gene delivery polynucleotide for stable insertion of a nucleic acid into a gene is provided. "Oligonucleotide" can be used interchangeable with nucleic acid and can refer to DNA or RNA, either double stranded or a single stranded piece or DNA or RNA. [0029] The nucleic acids described herein can have natural bases, modified bases and/or synthetic bases. Natural bases can include, for example, cytosine, guanine, adenine, thymine, uracil and pseudouracil. Modified bases can include, but are not limited to, xanthine and 2-deoxypseudoguanosine. Synthetic bases may include methyl-cytosine.

[0030] "Chimeric gene" as described herein refers to a combination of portions of one or more coding sequences to produce new genes. These mutations are distinct from fusion genes which merge whole gene sequences into a single reading frame and often retain their original functions. In some alternatives described herein, a chimeric gene comprising HDAg sequences is provided. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preSl derived sequence. A chimeric gene can be DNA or RNA.

[0031] "Chimeric protein" is a hybrid protein that is encoded by a nucleotide sequence spliced together from two or more complete or partial genes produced by recombinant DNA technology. Methods for creating a chimeric protein through chimeric genes is well known to those skilled in the art and can be performed with basic molecular cloning in which fragments of genes are combined with vector DNA to create the chimeric gene for protein expression.

[0032] "HDag" as described herein is hepatitis D antigen. In some alternatives described herein a chimeric gene comprising HDAg sequences is provided. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preSl derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HDAg genotype 1 B, HDAg genotype 2 A and/or HDAg genotype 2 B. A chimeric gene can be DNA or RNA. Shown in Figure 2 are the combined HDV- PreSl vaccine designs for Delta- 1 , Delta-2, Delta-3, Delta-4, Delta-5, Delta-6, Delta-7, Delta-8, Delta-9 and Delta- 10 for the chimeric genes described in the alternatives herein. These constmcts are used to encode the chimeric proteins described in the alternatives herein and are utilized for nucleic acid-based immunization by approaches described herein.

[0033] "Cleavage sequence" as described herein can refer to a self-cleaving 2A peptide. The chimeric genes can further encode at least one self-cleavage polypeptide sequence. Self-cleaving 2A polypeptide sequences, also referred to herein as self-cleavage sequences, sites or domains were first identified in the foot-and-mouth disease vims (Ryan, MD et al. (1991) "Cleavage of foot and mouth disease virus protein is mediated by residues located within a 19 amino acid sequence." J. Gen. Virol. 72(Pt 1 1):2727~2732). The 'cleavage' of a 2A peptide from its immediate downstream peptide is in fact affected by ribosomal skipping of the synthesis of the glycyl -prolyl peptide bond at the C-terminus of the 2A polypeptide (Lyan Lab Webpage: de Felipe P, Luke GA, Brown JD, Ryan MD (2010) Inhibition of 2A-mediated 'cleavage' of certain artificial polyproteins bearing N- terminal signal sequences. Biotechnol J 5: 213-223; Donnelly ML, Luke G, Mehrotra A, Li X, Hughes LE, et al. (2001 ) Analysis of the aphthovirus 2A/2B polyprotein 'cleavage' mechanism indicates not a proteolytic reaction, but a novel transiationai effect: a putative ribosomal 'skip' . J Gen Virol 82: 1013-1025). Several 2A self-cleavage polypeptides have been isolated (see, e.g., Szymczak AL, Vignali DA (2005) Development of 2A pepti de-based strategies in the design of multicistronic vectors. Expert Opin Biol Ther 5: 627-638, the disclosure of which is hereby incorporated by reference in its entirety). Four of the 2A polypeptide sequences identified to date have seen substantial use in biomedical research: picornavirus 2 A sequences FMDV 2 A (abbreviated herein as F2A); equine rhinitis A virus (ERAV) 2A (E2A); porcine teschovirus-1 2A (P2A), and insect vims Thosea asigna vims 2A (T2A), (de Felipe P, Luke GA, Hughes LE, Gani D, Halpin C, et al. (2006) E unum pluribus: multiple proteins from a self-processing polyprotein. Trends Biotechnol 24: 68-75).

[0034] Self-cleaving 2A sequences are preferred over alternative methods of expressing multiple proteins from a single construct, such as Internal Ribosomal Entry- Sequences (IRES), because of their short length and stoichiometric expression of multiple proteins flanking the 2A polypeptide (de Felipe P, Luke GA, Hughes LE, Gani D, Halpin C, et al. (2006) E unum pluribus: multiple proteins from a self-processing polyprotein. Trends Biotechnol 24: 68-75). In the alternatives described herein, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2A (P2A), foot-and-mouth disease virus (FMDV) 2 A (F2A), equine rhinitis A virus (ERAV) 2 A (E2A) and Thosea asigna virus 2 A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine-serine-glycine) motif at an N-terminus.

[0035] The Pre-Sl derived sequence, as described herein encodes the Pre- SI domain of the surface antigen of hepatitis B virus. Targeting of pre SI may be used to prevent both infections of HBV and HDV. It has been shown that a 48 amino acid stretch within the preS l region is effective in generating preS -specific antibodies. In some alternatives described herein, a chimeric gene comprising HDAg sequences is provided. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preS l derived sequence. In some alternatives, the at least one preS l derived sequence is pre SI A and/or preSl B.

[0036] "Codon optimization" as described herein, refers to a method for maximal protein selection by adaptation of codons of the transcript gene to the typical codon usage of a host. Those skilled in the art will appreciate that gene expression levels are dependent on many factors, such as promoter sequences and regulatory elements. As noted for most bacteria, small subsets of codons are recognized by tR A species leading to translational selection, which can be an important limit on protein expression. In this aspect, many synthetic genes can be designed to increase their protein expression level. The design process of codon optimization can be to alter rare codons to codons known to increase maximum protein expression efficiency. In some alternatives, codon selection is described, wherein codon selection is performed by using algorithms that are known to those skilled in the art to create synthetic genetic transcripts optimized for higher levels of transcription and protein yield. Programs containing algorithms for codon optimization are known to those skilled in the art. Programs can include, for example, OptimumGene™, GeneGPS® algorithms, etc. Additionally synthetic codon optimized sequences can be obtained commercially for example from Integrated DNA Technologies and other commercially available DNA sequencing services. In some alternatives, the chimeric gene comprises sequences, wherein at least one sequence is codon optimized. In some alternatives, the genes are codon optimized for expression in humans, which can include gene transcripts the core protein, HDAg, or at least one preSl derived sequence. The 2A and/or P2A sequences may or may not be codon optimized for expression in humans,

[0037] ^' 1 IB V core antigen" (HBcAg) or the nucleocapsid of HBV is an immunogenic particle composed of 180 subu its of a single protein chain. HBcAg has been disclosed as an immunogenic moiety that stimulates the T cell response of an immunized host animal . See, e.g, U.S. Pat. No. 4,818,527, U. S. Pat. No, 4,882, 145 and U.S. Pat. No. 5, 143,726, each of which is hereby incorporated by reference in their entirety. It can be used as a carrier for several peptidic epitopes covalently linked by genetic engineering as well as for chemically coupled protein antigens. (See Saliberg et al. (1998) Human Gene Therapy 9: 1719-29), in addition, HBcAg is non-cytotoxic in humans. Accordingly, it was contemplated that HBcAg is useful in genetic constructs for generating or enhancing an immune response to an accompanied target antigen (e.g., in constructs that encode a TCE derived from a pathogen),

[0038] Current listings of exemplary HBcAg sequences are publicly available at the National Center for Biotechnology Information (NCBI) world-wide web site. Several different HBcAg nucleic acid sequences (including novel HBcAg regions) can be utilized (e.g., humans, birds, such as stork or heron, or rodents such as ground squirrel or woodchuck). DNA obtained from a subject infected with HBV (e.g., humans, birds, such as stork or heron, or rodents such as ground squirrel or woodchuck) can also be isolated by PGR or another amplification technique.

[0039] For a review of PCR technology, see Molecular Cloning to Genetic Engineering White, B.A. Ed. in Methods in Molecular Biology 67: Humana Press, Totowa (1997) and the publication entitled "PCR Methods and Applications" (1991 , Cold Spring Harbor Laboratory Press). For amplification of mRNAs, it is within the scope of the invention to reverse transcribe n RNA into cDNA followed by PCR (RT-PCR): or, to use a single enzyme for both steps as described in U.S. Patent No. 5,322,770. Another technique involves the use of Reverse Transcriptase Asymmetric Gap Ligase Chain Reaction (RT-AGLCR), as described by Marshall R.L. et al. (PCR Methods and Applications 4:80-84, 1994),

[0040] The source of the HBcAg sequences that are included in the isolated nucleic acids described herein is not particularly limited. Accordingly, alternatives described herein may utilize an isolated nucleic acid that encodes an HBcAg derived from a hepatitis virus capable of infecting animals of any species, including but limited to, humans, non-human primates (e.g., baboons, monkeys, and chimpanzees), rodents, mice, reptiles, birds (e.g. , stork and heron), pigs, micro-pigs, goats, dogs and cats. In some alternatives, the HBcAg is selected from a human hepatitis antigen or an avian hepatitis antigen. Particularly preferred are the stork hepatitis antigen and a heron hepatitis antigen.

[0041] In certain alternatives, the HBcAg sequences described herein have variations in nucleotide and/or amino acid sequences, compared to native HBcAg sequences and are referred to as HBcAg variants or mutants. As used herein, the term "native" refers to naturally occurring HBV sequences (e.g., available HBV isotypes). Variants may include a substitution, deletion, mutation or insertion of one or more nucleotides, amino acids, or codons encoding the HBcAg sequence, which may result in a change in the amino acid sequence of the HBcAg polypeptide, as compared with the native sequence. Variants or mutants can be engineered, for example, using any of the techniques and guidelines for conservative and non-conservative mutations set forth, for instance, in U. S. Patent No. 5,364,934, which is hereby incorporated by reference in its entirety.

[0042] Accordingly, when the term "consisting essential ly of is used, in some contexts, variants or mutants of an HBcAg sequence or of a particular antigen sequence are intended to be encompassed. That is, in some contexts and in some alternatives, the variants or mutants of the sequences disclosed herein are equivalents because the variation or mutation in sequence does not change or materially affect the basic and novel characteristics of the claimed invention.

[0043] A codon-optimized HBcAg can, in some alternatives, be encoded within the isolated nucleic acid or chimeric gene. A codon-optimized sequence may, in some alternatives, be obtained by substituting codons in an existing sequence with codons more frequently used in the intended host subject (e.g., a human).

[0044] Some alternatives include, for example, one or more of the HBcAg nucleic acid or protein sequences disclosed in International Patent Application Publication Number WO 20091 130588, published December 7, 201 1, which designated the United States and was published in English, the disclosure of which i s hereby expressly incorporated by reference in its entirety. In some alternatives, a chimeric gene encoding HBV core (HBcAg) is provided. In some alternatives, the chimeric gene comprises a sequence set forth in SEQ ID NO' s: 60, 62, 65, 67, 70 or 72.

DETAILED DESCRIPTION

[0045] Existing therapies with reversed transcriptase (RT) inhibitors effectively supress HBV replication but fails to induce off-therapy responses, and have no effect on HDV replication. The viroid-like virus HDV is a highly pathogenic virus and can only complete its replication cycle in ceils infected by HBV. HDV lacks its own gene for a viral envelope protein and therefore "steals" the envelope of HBV, the hepatitis B surface antigen (HBsAg), when leaving the cell. Hence, the HBV vaccine can protect naive individuals from both HBV and HDV, but cannot protect a person infected by HBV against HDV superinfection due to the inherent overproduction of HBsAg during the HBV infection,

[0046] In some alternatives described herein, preS 1 antibodies were shown to prevent HBV and HDV infection. Importantly, both HBV and HDV require the same preSl sequence to enter hepatocvtes. Thus, targeting preSl is an excellent way to prevent both infections. It has been shown that a 48 amino acid stretch within the preSl region is effective in generating preS l -specific antibodies. In some alternatives described herein, pre SI antibodies can be induced by a chimeric HBV core antigen (HBcAg) protein exposing a preS l sequence (aa 1-42) on the surface. In addition, HDAg was shown to induce genotype-specific T cell responses in mice. This suggests that multiple genotypes must be contained in an HDAg-based vaccine.

[0047] Additionally, it has been discovered that hepatitis B core antigen (HBcAg) is a potent adjuvant that improves the immune response of a subject to a coadministered antigen (See, e.g., PCT Publication No. WO 2010/086743 A2, published August 5, 2010, which is hereby incorporated by reference in its entirety). In the present disclosure, it is contemplated that a nucleic acid encoding HBcAg improves the immune response of a mammal to the second polypeptide antigen.

[0048] Accordingly, some alternatives include methods of enhancing or improving an immune response of a subject, wherein a nucleic acid encoding an HBcAg, preferably codon-optimized for expression in humans, is provided to a subject along with another chimeric gene comprises at least two HDAg sequences, which are also preferably codon-optimized for expression in humans. In some alternatives, a chimeric gene encoding a HDV polypeptide with a pre-Sl domain is provided. The pre-Sl domain, as described herein, can allow prevention of HBV and HDV infections. In some alternatives, the at least one preSl derived sequence is preSl A and comprises an amino acid sequence set forth in SEQ ID NO: 1 . In some alternatives, the at least one preSl derived sequence is preSl B and comprises an amino acid sequence set forth in SEQ ID NO: 2. In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, preS l B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6.

[0049] The HDV infection cannot be prevented in patients infected by HBV using the current HBsAg-based vaccines lacking both preSl and preS2. Thus, a combined approach with vaccines containing both parts of preSl that induces neutralising antibodies, and parts or the whole HDAg to induce HDV-specific T cells should be able to inhibit, ameliorate, treat or prevent HDV infection in HBV infected patients.

[0050] Several alternatives described herein concern isolated chimeric genes, expression constructs, DNA immunogenic compositions, DNA vaccines or nucleic acid immunogens, preferably, which are codon-optimized for expression in humans, and that encode a peptide that comprises, consists of, or consists essentially of at least two antigenic sequence, which is an HDV sequence. In some alternatives a chimeric gene is also contemplated, which can encode HBcAg, preferably from avian, stork or heron, which is codon optimized for expression in humans.

Chimeric genes

Chimeric genes for expression of HDAg protein domains.

[0051] Provided herein are chimeric genes comprising HDAg sequences and chimeric genes encoding HBV core antigen (HBcAg). In some alternatives, a chimeric gene comprising HDAg sequences and a sequence encoding a preSl domain is provided.

The chimeric gene can comprise at least two sequences encoding hepatitis D antigen

(HDAg), at least one cleavage sequence and at least one preSl derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding

HDAg genotype 1 A, HDAg genotype 1 B, HDAg genotype 2 A and/or HDAg genotype 2

B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2A

(P2A), foot-and-mouth disease vims (FMDV) 2A (F2A), equine rhinitis A virus (ERAV)

2A (E2A) and Thosea asigna virus 2A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine- serine-glycine) motif at an N-terminus. In some alternatives, the at least one preSl derived sequence is preSl A and/or preSl B. In some alternatives, preSl A comprises an amino acid sequence set forth in SEQ ID NO: 1 . In some alternatives, preSl B comprises an amino acid sequence set forth in SEQ ID NO: 2.

In some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4. In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, preS l B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 10. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 15. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 17. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 20. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 22. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 25. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 21. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 30. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ) ID NO: 32. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 35, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 37. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 40. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 45. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 47. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 52. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 55, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 57. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59. In some alternatives, the chimeric gene is codon optimized. Preferably, this sequence is codon optimized for expression in humans.

[0052] The preSl peptides that are used are shown in Figure 1, which is an alignment of the preS 1 peptides of HBV. As shown in Figure 2 are the combined HDV- PreSl vaccine designs for Delta- 1, Deita-2, Deita-3, Delta-4, Delta-5, Deita-6, Delta-7, Delta-8, Delta-9 and Delta- 10 for the chimeric genes described in the alternatives herein. These constructs are used to encode the chimeric proteins described herein.

Chimeric genes for expression of HBV Core protein

[0053] Described herein are chimeric genes for the expression of HBV core. In some alternatives, a chimeric gene for expressing HBV core antigen is provided, wherein the chimeric gene comprises a sequence encoding an HBV core antigen. In some alternatives, the chimeric gene comprises a sequence set forth in SEQ ID NO's: 60, 62,

65, 67, 70 or 72. In some alternatives, the chimeric gene is codon optimized for expression in humans. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO's 64, 69 or 74.

Preferably, this sequence is codon optimized for expression in humans. Chimeric i I D An proteins

[0054] Chimeric proteins encoded by the chimeric genes described herein are provided, hi some alternatives a chimeric protein comprising at least two HDAg protein domains, encoded by the chimeric genes of anyone of the alternatives described herein is provided. The chimeric gene can compri se at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preS l derived sequence.

In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HDAg genotype 1 B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consi sting of porcine teschovirus-1 2A (P2A), foot-and-mouth disease virus (FMDV) 2A (F2A), equine rhinitis

A virus (ERAV) 2 A (E2A) and Thosea asigna virus 2 A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine-serine-glycine) motif at an N- terminus. In some alternatives, the at least one preS l derived sequence is preS l A and/or pre SI B. In some alternatives, preS l A comprises an amino acid sequence set forth in

SEQ ID NO: 1 . In some alternatives, preS l B comprises an amino acid sequence set forth in SEQ ID NO: 2. In some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. in some alternatives, the sequence encoding HDAg genotype 1 B compri ses a nucleic acid sequence set forth in

SEQ ID NO: 4. In some alternatives, preS l A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, pre SI B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ

ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding

HDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2

B and comprises a sequence set forth in SEQ) ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 10. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 15. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 17. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 20. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 22. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ) ID NO: 25, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 21. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 30. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 32. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 35. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 37. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 40. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ) ID NO: 45, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 47. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 52. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ 03 NO: 55. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 57. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59. In some alternatives, the chimeric gene is codon optimized for expression in humans.

Chimeric HBV Core (HBcAg)

[0055] In some alternatives described herein, a chimeric protein comprising HBV core or an antigenic or immunogenic portion thereof (e.g., a portion that improves an immunological response to a co-administered nucleic acid, such as a portion that promotes an adjuvant activity with respect to a co-administered nucleic acid). In some alternatives, the HBV Core or an antigenic or immunogenic portion thereof is a human HBV Core or an antigenic or immunogenic portion thereof, a rodent HBV Core or an antigenic or immunogenic portion thereof, such as a woodchuck or ground squirrel HBV Core or antigenic or immunogenic portion thereof, or an avian HBV Core or an antigenic or immunogenic portion thereof, such as a stork or heron HBV Core or an immunogenic portion thereof is provided. The protein can be encoded by any one of the chimeric genes encoding HBV core or an antigenic portion thereof described herein. In some alternatives, the chimeric gene comprises a sequence encoding an HBV core antigen or an antigenic portion thereof. In some alternatives, the chimeric gene comprises a sequence set forth in SEQ ID NO's: 60, 62, 65, 67, 70 or 72 or an antigenic or immunogenic portion thereof. In some alternatives, the chimeric gene is codon optimized for expression in humans. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO's 64, 69 or 74 or an antigenic or immunogenic portion thereof.

[0056] Accordingly, several aspects of the invention described herein concern compositions that comprise, consist essentially of, or that consist of chimeric genes that encode an HDAg which may be codon-optimized for expression in humans, and, which can be joined (e.g., in Cis) to a nucleic acid (preferably codon-optimized for expression in an animal or human) that encodes at least one preSl derived sequence. The sequence can further comprise a self-cleavage sequence or domains (e.g., P2A, T2A, E2A, or F2A) that exist between the nucleic acid encoding the target antigen and the nucleic acid encoding the HDAg, and, which may optionally, exist within the nucleic acid sequence encoding the HDAg polypeptide such that the translated HDAg is self-cleaved into polypeptide fragments. Preferably, one or more or all of these sequences are codon optimized for expression in humans. Methods of using the foregoing immunogenic compositions to generate an immune response (e.g., a T ceil and/or antibody specific immune response) or to inhibit, ameliorate, treat, or prevent HBV and HDV infection in a subject, preferably a human and, optionally a chronically infected human, are contemplated alternatives. Optionally, a subject can be identified as one in need of an immune response to HB V and HDV prior to administration of the composition and/or said subject can be evaluated for the immune response or viral clearance after administration of said compositions and such identification and/or evaluation can be accomplished using readily available diagnostics and/or clinical approaches.

[0057] Compositions or mixtures that further comprise, consist essentially of, or that consist of one or more of nucleic acids (e.g., in Trans) that encode polypeptide adjuvants, such as nucleic acids encoding IL-12, IL-1.5, or IL-21, which may optionally be codon optimized for expression in humans, or that consist of polypeptide adjuvants IL-12, :\ or IL-21 or that consist of small molecule adjuvants such as ribavirin or CpG nucleic acids are also alternatives. Preferably, these nucleic acids are codon optimized for expression in humans and these nucleic acids can be used as an immunogen to inhibit, ameliorate, treat, or prevent HBV and HDV infection. Methods of using the aforementioned compositions to improve, enhance, or generate an immune response in a subject or to treat diseases such as HBV and HDV, especially in chronically infected individuals, are also contemplated,

[0058] In some alternatives, the compositions can comprise proteins encoded by the chimeric genes. Furthermore compositions comprising chimeric genes and the chimeric proteins are also contemplated. The composition can comprise chimeric genes encoding at least one HDAg and/or chimeric genes encoding hepatitis B core. In some alternatives, the compositions comprise chimeric proteins. The chimeric proteins can comprise the Delta-1, Delta-2, Delta-3, Delta-4, Delta-5, Delta-6, Delta-7, Delta-8, Delta- 9, Delta- 10 and/or any of the Core constructs as described herein and/or in Figures 2 and 3.

[0059] In some alternatives, the HDAg sequence comprises a sequence set forth in SEQ ID NO's 3, 4, 8 or 9, In some alternatives, the sequences are codon optimized for expression in humans. In some alternatives, the nucleic acid sequence encodes greater than or equal to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% of the HDAg polypeptide or an amount that is within a range defined by any two of the aforementioned percentages. Optionally, these sequences can be codon optimized for expression in humans. In some alternatives, the nucleic acid sequence encodes greater than or equal to or any number in between 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 1 11, 1 12, 113, 1 14, 115, 116, 1 17, 118, 1 19, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141 , 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, or 195 amino acid residues of the HDAg polypeptide or an amount that is within a range defined by any two of the aforementioned percentages. In some alternatives, the nucleic acid encodes a full length HDAg polypeptide. Optionally, these sequences can be codon optimized for expression in humans. Methods of using the foregoing compositions to generate an immune response (e.g., a T cell and/or antibody specific immune response) or to inhibit, ameliorate, treat, or prevent an HBV and HDV infection in a subject, preferably a human and, optionally a chronically infected human, are contemplated alternatives. Optionally, a subject can be identified as one in need of an immune response to HBV and HDV prior to administration of the composition and/or said subject can be evaluated for the immune response or viral clearance after administration of said compositions and such identification and/or evaluation can be accomplished using readily available diagnostics and/or clinical approaches. [0060] In some alternatives, the self-cleavage polypeptide exists after amino acid residue number 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 1 11, 1 12, 113, 1 14, 115, 116, 1 17, 118, 1 19, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141 , 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, or 195 of the HDAg polypeptide. Optionally, these sequences can be codon optimized for expression in humans. In some alternatives, the self-cleavage polypeptide exists before amino acid residue number 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61 , 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, i l l , 112, 1 13, 1 14, 115, 1 16, 117, 1 18, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161 , 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 1 78, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191 , 192, 193, 194, or 195 of the HDAg polypeptide. Optionally, these sequences can be codon optimized for expression in humans. Methods of using the foregoing compositions to generate an immune response (e.g., a T cell and/or antibody specific immune response) or to inhibit, ameliorate, treat, or prevent HBV and HDV in a subject, preferably a human and, optionally a chronically infected human, are contemplated alternatives. Optionally, a subject can be identified as one in need of an immune response to HBV and HDV prior to administration of the composition and/or said subject can be evaluated for the immune response or viral clearance after administration of said compositions and such identification and/or evaluation can be accomplished using readily available diagnostics and/or clinical approaches. [0061] In some alternatives a composition that comprises anyone or more of the chimeric genes described herein, wherein the chimeric genes encode at least at least- two HDAg protein domains, is provided. In some alternatives, the chimeric gene comprises HDAg sequences, wherein the chimeric gene comprises at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preSl derived sequence. In some alternatives, the composition comprises a protein encoded by anyone or more of the chimeric genes provided herein.

[0062] In some alternatives a composition comprising anyone or more of the chimeric genes encoding HBcAg is provided. In some alternatives, the chimeric gene comprises a sequence encoding an HBV core antigen. In some alternatives, the composition comprises a protein encoded by anyone or more of the chimeric genes provided herein.

[0063] In some alternatives a composition comprising a protein encoded by anyone or more of the chimeric genes is provided. In some alternatives, the composition further comprises a chimeric gene of any one or more of the alternatives provided herein.

[0064] In some alternatives, the composition further comprises the chimeric protein of anyone of the alternatives described herein. In some alternatives, the composition further comprises an adjuvant. In some alternatives, said adjuvant comprises a nucleic acid encoding a polypeptide adjuvant. In some alternatives, said polypeptide adjuvant is IL-12, IL-15, or IL-21 , In some alternatives, said adjuvant is ribavirin or a CpG-containing nucleic acid. In some alternatives, said adjuvant is a polypeptide. In some alternatives, said adjuvant comprises an adjuvant promoting portion or subunit of IL-12, IL-15, or IL-21.

[0065] In some alternatives, the composition is present or provided in an injection device or an injection device configured to be used in conjunction with an eiectroporation device.

Methods for using the chimeric gene or composition

[0066] In some alternatives, the chimeric gene or composition of any one of the alternatives is for use in providing an immunogenic composition, generating an immune response in a subject, or for DNA vaccination so as to inhibit, ameliorate, treat, or prevent HBV and HDV infection. In some alternatives, the chimeric gene, chimeric protein or composition is for use in generating an antibody, T-lymphocyte or CTL- specific response in a subject so as to prevent an HBV and HDV infection. In some alternatives, the chimeric gene, chimeric protein or composition of any one of the alternatives described herein is for immunogen delivery so as to inhibit, ameliorate, treat, or prevent HBV and HDV in a subject that has been identified as having and HDV or HBV infection.

[0067] In some alternatives, a method of eliciting an immune response is provided wherein the method comprises administering to a subject having HDV infection and/or HBV infection the nucleic acid or composition of any one of the alternatives at a first time. In some alternatives, said administering comprises injecting said nucleic acid into a patient, such as using an IVIN needle with or without electroporation. In some alternatives, the method further comprises administering a second administration of a nucleic acid or composition of any one of the alternatives described herein is provided. In some alternatives, the method further comprises providing an adjuvant. In some alternatives, said adjuvant is a nucleic acid encoding a polypeptide adjuvant, such as IL- 12, IL-15, or IL-21. In some alternatives, said adjuvant is IL-12, EL-15, or IL-21. In some alternatives, said second administration is given after said first time. In some alternatives, said adjuvant is given before, during, or after administration of said nucleic acid or composition of any one of the alternatives described herein. In some alternatives, said second administration is given one week, two weeks, three weeks, four weeks, five weeks, or six weeks after the first administration of said nucleic acid or composition of any one of the alternatives described herein.

[0068] In some alternatives, a method of inhibiting, ameliorating, treating, or preventing hepatitis D virus in a subject in need is provided, wherein the method compri ses administering the composition of anyone or more of the alternatives described herein to the subject in need. In some alternatives, the subject has been identified as a person at risk of contracting HDV or a person having HDV.

[0069] In some alternatives, a method of increasing preSl antibodies in a subject in need is provided, wherein the method comprises administering the compositions of anyone of the alternatives to the subject in need. In some alternatives, the method further comprises administering the composition of anyone of the alternatives described herein to the subject in need.

[0070] Various routes of administration may be used for the methods described herein. In some alternatives, the immunogenic composition is administered pareiiterallv (e.g., intramuscularly, intraperitoneally, subcutaneously, or intravenously to a mammal subject). In a preferred alternative, the immunogenic compositions are administered intramuscularly, derm ally, or subcutaneously. The methods may also include applying electrical stimulation, which can enhance the administration of the immunogenic compositions. As an example, electroporation may be included in the present methods disclosed herein. Electroporation includes applying electrical stimulation to improve the permeability of cells to the administered composition. Examples of electroporation techniques are disclosed in U.S. Patent Nos. 6,610,044 and 5,273,525, the disclosures of both of these references are hereby incorporated by reference in their entireties,

[0071] The concentration of the nucleic acid or protein in the immunogenic composition to be administered can vary from 0.1 ng ml to 50 mg/ml. In some aspects, the concentration of the immunogenic composition administered (e.g., a suitable dose of nucleic acid or protein for administration) is between 10 ng/ml to 25 mg/ml. In still other aspects, the concentration is between 100 ng/ml to 10 mg ml. In some aspects, the suitable dose of nucleic acid or protein for administration is greater than or equal to or less than 100 ng/ml, 150 ng/ml, 200 ng/ml, 250 ng/ml, 300 ng/ml, 350 ng/ml, 400 ng/ml, 450 ng/ml, 500 ng ml, 550 ng/ml, 600 ng/ml, 650 ng/ml, 700 ng/ml, 750 ng/ml,, 800 ng/ml, 850 ng/ml, 900 ng/ml, 950 ng/ml, 1 _ug/ml, 2 ^ig/ml, 3 ^ig/ml, 4 μg/ml, 5 _ug/ml, 6 μ¾/ηι1, 7 μg/ml, 8 μ¾''ηι1, 9 μ&'ΊηΙ, 10 μ§'Ίη1, 11 μg/mi, 12 μg/ml, 13 μ¾/ιη1, 14 μg/ml, 15 μ¾/ηι1, 16 μg/ml, 17 μ¾''ηι1, 18 μg/ml, 19 μg/ml, 20 μg/ml, 21 μ§'Ίη1, 22 μg/ml, 23 μg/ml, 24 μg/ml, 25 μg/ml, 26 μg/ml, 27 μg/ml, 28 μg/ml, 29 μ^'ιηΐ, 30 μg/ml, 31 μg/ml, 32 pg-'ml, 33 μg/ml, 34 μg/ml, 35 μg/ml, 36 pg/ml, 37 g/ml, 38 μg/mi, 39 μg/ml, 40 μg/ml, 41 μg/ml, 42 μg/ml, 43 μ.g/ml, 44 μg/ml, 45 μ^'τηΐ, 46 μ§/ηι1, 47 μg/ml, 48 μg/ml, 49 μ§/ηι1, 50 μ§/π , 55 μg/rnl, 60 μ /πιΐ, 65 μg/ml, 70 g/ml, 75 pg/ml, 80 μg/ml, 85 g/ml, 90 μ¾''ηι1, 95 μg/ml, 100 200 μg/ml, 250 μg/ml, 300 μg/ml, 350 μg/ml, 400 μ¾''ηι1, 450 μ¾''ηι1, 500 μg/ml, 550 μg/ml, 600 μg/ml, 650 μg/ml, 700 750 μg/ml„ 800 μg ml, 850 μg/mi, 900 μg/ml, 950 μg/mi, 1.0 mg/ml, 1.1 mg/ml, 1.2 mg/ml, 1.3 mg/ml, 1.4 mg/ml, 1.5 mg/ml, 1.6 mg/ml, 1.7 mg/ml, 1.8 mg/ml, 1.9 mg/ml, 2.0 mg/ml, 2.1 mg/ml, 2.2 mg/ml, 2.3 mg/ml, 2.4 mg/ml, 2.5 mg/ml, 2.6 mg/ml, 2.7 mg/ml, 2.8 mg/ml, 2.9 mg/ml, 3.0 mg/ml, 3. 1 mg/ml, 3.2 mg/ml, 3.3 mg/ml, 3.4 mg/ml, 3.5 mg/ml, 3.6 mg/ml, 3.7 mg/ml, 3.8 mg/ml, 3.9 mg/ml, 4.0 mg/ml, 4.1 mg/ml, 4.2 mg/ml, 4.3 mg/ml, 4.4 mg/ml, 4.5 mg/ml, 4.6 mg/ml, 4.7 mg/ml, 4.8 mg/ml, 4.9 mg/ml, 5.0 mg/ml, 5.1 mg/ml, 5.2 mg/ml, 5.3 mg/ml, 5.4 mg/ml, 5.5 mg/ml, 5.6 mg/ml, 5.7 mg/ml, 5.8 mg/ml, 5.9 mg/ml, 6.0 mg/ml, 6.1 mg/ml, 6.2 mg/ml, 6.3 mg/ml, 6.4 mg/ml, 6.5 mg ml, 6.6 mg/ml, 6.7 mg/ml, 6.8 mg/ml, 6.9 mg/ml, 7.0 mg/ml, 7.1 mg/ml, 7.2 mg/ml, 7.3 mg/ml, 7.4 mg/ ^' ml, 7.5 mg/ml, 7.6 mg/ml, 7.7 mg/ml, 7.8 mg/ml, 7.9 mg/ml, 8.0 mg ml, 8.1 mg/ml, 8.2 mg/ml, 8.3 mg/ml, 8.4 mg/ ^' ml, 8.5 mg/ml, 8.6 mg/ml, 8.7 mg/ml, 8.8 mg/ml, 8.9 mg/ml, 9.0 mg/ml, 9.1 mg/ml, 9.2 mg/ml, 9.3 mg/ml, 9.4 mg/ml, 9.5 mg ml, 9.6 mg/ml, 9.7 mg/ml, 9.8 mg/ml, 9.9 mg/ml, 10.0 mg/ml, 1 1 mg/ml, 12 mg/ml, 13 mg/ml, 14 mg/ml, 15 mg/ml, 16 mg/ml, 1 7 mg/ml, 18 mg/ml, 9 mg/ml, 20 mg/ml, 21 mg/ml, 22 mg ml, 23 mg/ml, 24 mg ml, 25 mg/ml, 26 mg ml, 27 mg/ml, 28 mg/ml, 29 mg/ml, 30 mg ml, 31 mg/ml, 32 mg ml, 33 mg/ml, 34 mg ml, 35 mg/ml, 36 mg/ml, 37 mg/ml, 38 mg ml, 39 mg/ml, 40 mg ml, 41 mg/ml, 42 mg ml, 43 mg/ml, 44 mg/ml, 45 mg/ml, 46 mg/ml, 47 mg/ml, 48 mg/ml, 49 mg/ml, 50 mg/ml, or an amount within a range defined by, and including, any two of these values.

[0072] The amount of the chimeric gene or protein administered using the methods described herein can vary from 1 ng to lOg. In some aspects, the amount of nucleic acid or protein contained administered is less than greater than or equal to 1 ng, 5 ng, 10 ng, 20 ng, 30 ng, 40 ng, 50 ng, 60 ng, 70 ng, 80 ng, 90 ng, 100 ng, 150 ng, 200 ng, 250 ng, 300 ng, 350 ng, 400 ng, 500 ng, 600 ng, 700 ng, 800 ng, 900 ng, 1 ^igl μg, 2 μg, 3 μg, 4 μ¾ 5 μ¾ 6 μ¾ 7 μ¾ 8 μ¾ 9 μg, 10 μg, 1 1 μg, 12 μg, 13 μg, 14 μg, 15 μg, 16 μg, 17 μg, 18 μg, 19 μg, 20 μg, 21 μg, 22 μg, 23 μg, 24 μg, 25 μg, 26 μg, 27 μg, 28 μg, 29 μg, 30 μg, 31 μg, 32 μg, 33 μg, 34 μg, 35 μg, 36 μg, 37 μg, 38 μg, 39 μg, 40 μg, 41 μg, 42 μg, 43 μ& ⁴⁴ μ& ⁴⁵ μ& ⁴⁶ μ& ⁴⁷ μ& ⁴ » μβ, 49 μ.g, 50 μg, 55 μ¾ 60 μg, 65 μ¾ 70 μg, 75 μ¾ 80 μ¾ 85 μ¾ 90 μg, 95 μg, 100 μg, 105 μg, 110 μg, 115 μg, 120 μg, 125 μg, 130 μg, 135 μg, 140 μ^ 145 μg 150 μg, 155 μg, 160 μg, 165 μg, 170 μg, 175 μg, 180 μg, 185 μg, 190 μg, 195 μg 200 μg, 205 μg, 210 μg, 215 μg, 220 μg, 225 μg, 230 μg, 235 μg, 240 μg, 245 [ig 250 μg, 255 ng, 260 μg, 265 μg, 270 μg, 275 μg, 280 \ig, 285 μg, 290 μg, 295 μ¾ 300 μg, 305 μg, 310 μg, 315 ng, 320 ng, 325 ng, 330 μg, 335 μg, 340 μg, 345 μg 350 ng, 355 ng, 360 μ¾ 365 μ¾ 370 ng, 375 ng, 380 ng, 385 ng, 390 μ¾ 395 μg 400 μg, 405 μg, 410 μg, 415 ig, 420 μ¾ 425 ng, 430 ng, 435 ng, 440 μ¾ 445 μg 450 μg, 455 μg, 460 μg, 465 μg, 470 μg, 475 μg, 480 μg, 485 μg, 490 μ& 495 μg 500 μg, 505 μg, 510 μg, 515 μg, 520 g, 525 μg, 530 μg, 535 μ¾ 540 μ¾ 545 μg 550 μg, 555 μg, 560 μg, 565 μg, 570 μg, 575 μg, 580 μg, 585 μ¾ 590 μ¾ 595 μg 600 μg, 605 μg, 610 μg, 615 μg, 620 μg, 625 μg, 630 μg, 635 μg, 640 μ¾ 645 μg 650 μg, 655 μg, 660 μg, 665 μg, 670 μg, 675 μg, 680 μg, 685 μg, 690 μg, 695 μg, 700 μg, 705 ng, 710 μg, 715 μg, 720 ng, 725 μg, 730 ng, 735 μg, 740 μg, 745 ig 750 pg, 755 ug, 760 μ¾ 765 μ ₈ , 770 μ ₈ , 775 μ _§ , 780 g, 785 μ¾ 790 μ ₈ , 795 μ _§ , 800 μ¾ 805 μ¾ 810 μ¾ 815 μ§, 820 μ& 825 μg, 830 μ¾ 835 μ¾ 840 μ§, 845 pg 850 μg, 855 μ¾ 860 μ¾ 865 μ¾ 870 μ¾ 875 μ¾ 880 μ¾ 885 ug, 890 μ¾ 895 μ§ 900 μ¾ 905 μg, 910 μg, 915 μ¾ 920 μ¾ 925 μg, 930 μ¾ 935 μg, 940 μ¾ 945 μg 950 μg, 955 μg, 960 μ& 965 μg, 970 μg, 975 μg, 980 μg, 985 μg, 990 μg, 995 μg, 1.0 mg, 1.1 mg, 1.2 nig, 1.3 mg,

1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2.0 mg, 2.1 mg, 2.2 mg, 2.3 mg, 2.4 mg,

2.5 mg, 2.6 mg, 2.7 mg, 2.8 mg, 2.9 mg, 3.0 mg, 3.1 mg, 3.2 mg, 3.3 mg, 3.4 mg, 3.5 mg,

3.6 mg, 3.7 mg, 3.8 mg, 3.9 mg, 4.0 mg, 4.1 mg, 4.2 mg, 4.3 mg, 4.4 mg, 4.5 mg, 4.6 mg,

4.7 mg, 4.8 mg, 4.9 mg, 5.0 mg, 5.1 mg, 5.2 mg, 5.3 mg, 5.4 mg, 5.5 mg, 5.6 mg, 5.7 mg,

5.8 mg, 5.9 mg, 6.0 mg, 6.1 mg, 6.2 mg, 6.3 mg, 6.4 mg, 6.5 mg, 6.6 mg, 6.7 mg, 6.8 mg,

6.9 mg, 7.0 mg, 7.1 mg, 7.2 mg, 7.3 mg, 7.4 mg, 7.5 mg, 7.6 mg, 7.7 mg, 7.8 mg, 7.9 mg,

8.0 mg, 8.1 mg, 8.2 mg, 8.3 mg, 8.4 mg, 8.5 mg, 8.6 mg, 8.7 mg, 8.8 mg, 8.9 mg, 9.0 mg,

9.1 mg, 9.2 mg, 9.3 mg, 9.4 mg, 9.5 mg, 9.6 mg, 9.7 mg, 9.8 mg, 9.9 mg, 10.0 mg, 1 1 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg, 30 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, Ig, 2g, 3g, 4g, 5g, 6g, 7g, 8g, 9g, 1 Og or within a range defined by, and including, any two of these values.

Materials and Methods.

[0073] Ei some alternatives, compositions are employed and methods performed according to the descriptions below. Other materials and methods are contemplated and consistent with the disclosure herein. Accordingly, the disclosure below should be read as enabling but not limiting to the claimed subject matter.

[0074] Materials and methods are drawn from Holmstrom et a!., (2013) "A Synthetic Codon-Optimized Hepatitis C Polyfunctional CDS + T Cell Responses in Virus Nonstructural 5 A DNA Vaccine Primes Wild-Type and NS 5 A- Transgenic Mice" J Immunol 190: 1 1 3-1 124, prepublished online January 2, 2013, which is hereby incorporated by reference in its entirety for all content from pages 1 13-1 124.

[0075] The following sections are provided to illustrate various alternatives of the present invention. It is to be understood that the following discussion is not comprehensive or exhaustive of the many types of alternatives, which can be prepared in accordance with the present invention.

[0076] In some embodiments the methods described herein comprises delivering to an intracellular space, such as a plurality of muscle cells, of said subject the chimeric gene, chimeric protein or compositions of the alternatives herein. In some embodiments this method comprises delivering to an intracellular space such as a plurality of muscle ceils or intradermally of said subject an HBcAg chimeric protein or HDAg chimeric protein or a chimeric gene encoding HDag chimeric protein or HBCAg chimeric proteins as described herein. In some embodiments this method comprises HBcAg chimeric protein encoded by a chimeric gene, and the polynucleotide is delivered to an intracellular space such as a plurality of muscle cells or intradermally of an animal and translated into an HBcAg chimeric protein therein, thereby delivering said HBcAg chimeric protein to said subject. In some alternatives, this method comprises HDAg chimeric protein encoded by a chimeric gene, and the polynucleotide is delivered to an intracellular space such as a plurality of muscle cells or intradermally of an animal and translated into an HDAg chimeric protein therein, thereby delivering said HDAg chimeric protein to said subject. As the HDAg chimeric proteins described herein further comprise a Pre SI A/B domain, this can be used to inhibit, ameliorate, treat, or prevent HBV and/or HDV infections. In some embodiments the components of said immunogenic composition are delivered in a single injection. In some embodiments the components of said immunogenic composition are delivered in two or more injections. In some embodiments this method comprises providing ribavirin to said subject. In some embodiments this method comprises providing pegyiated interferon to said subject. In some embodiments the pegyiated interferon is pegyiated interferon ct2a. In some embodiments a boost vaccination is administered within 28 days of the administration of said chimeric gene.

Preferred Constructs and Evaluation for Immunogenicity

[0077] Preferred expression constructs comprising one or more of the genes described herein (see e.g., FIGURE 2 AND 3, and chimeric genes of or encoding proteins as set forth in SEQ ID NOs: 1-74) are tested in animals to confirm that the introduction of self-cleavage sites into the fusion proteins encoded by the administered nucleic acids improve the immunogenicity (e.g., T cell and/or antibody response of the subject) of the immunogenic compositions. The immunogenicity of several constructs are evaluated after introducing the constructs into animals using the IVEN injector with electroporation (see PCT/1B2012/001321, WO 2012/172424 Al), which was published in English on December 20, 2012 and designated the United States, hereby expressly incorporated by reference in its entirety). In a first set of experiments, the following constructs are evaluated:

[0078] (1) expression constructs comprising a chimeric encoding a wild-type HDAg (i.e. HDAg gt 1 A/B, HDag gt 2 A/B, HDAg-L or HDAg-S) sequence or both, and at least one pre- SI sequence,

[0079] (2) expression constructs comprising a nucleic acid encoding a HDAg (i.e. HDAg gt 1 A/B, HDag gt 2 A/B, HDAg-L or HDAg-S) sequence or both, and at least one pre-Sl sequence wherein said nucleic acid is codon optimized for expression in humans;

[0080] (3) expression constructs comprising a nucleic acid encoding a HDag (i.e. HDAg gt 1 A/B, HDag gt 2 A B, HDAg-L or HDAg-S) sequence or both, and at least one pre-Sl sequence wherein said nucleic acid is codon optimized for expression in humans and wherein said nucleic acid additionally encodes a self-cleavage sequence, which may also be codon optimized for expression in humans (e.g., P2A, E2A, F2A, or T2A with or without GSG modification).

[0081] (4) expression constructs comprising a nucleic acid encoding a HDAg (i.e. HDAg gt 1 A B, HDag gt 2 A/B, HDAg-L or HDAg-S) sequence or both, wherein said nucleic acid is codon optimized for expression in humans and wherein said nucleic acid, optionally encodes a self-cleavage sequence, which may also be codon optimized for expression in humans (e.g., P2A, E2A, F2A, or T2A with or without GSG modification) within said i.e. HDAg gt 1 A/B, HDag gt 2 A/B, HDAg-L or HDAg-S sequence or both or at the N or C terminus of said i.e. HDAg gt 1 A/B, HDag gt 2 A B, HDAg-L or HDAg-S sequence or both. These expression construct can also be administered with an expression construct that comprises a nucleic acid sequence encoding an HBcAg, which may also be codon optimized for expression in humans (e.g., a codon optimized stork or heron HBcAg)

[0082] (5) expression constructs comprising a nucleic acid encoding a i.e. HDAg gt I A B, HDag gt 2 A B, HDAg-L or HDAg-S sequence or both, wherein said nucleic acid is codon optimized for expression in humans and, wherein said nucleic acid, optionally encodes a self-cleavage sequence, which may also he codon optimized for expression in humans (e.g., P2A, E2A, F2A, or T2A with or without GSG modification) within said e.g., HDAg gt 1 A/ ^' B, HDag gt 2 A/B, HDAg-L or HDAg-S sequence or both or at the N or C terminus of said HDAg-L or said HDAg-S sequence or both. Additionally the expression construct may be administered with another expression construct which comprises a nucleic acid sequence encoding an HBcAg, which may also be codon optimized for expression in humans (e.g., a codon optimized stork or heron HbcAg).

[0083] Assays are then performed to determine the relative impact of having self-cleavage polypeptide sequences in the constructs encoding the HBcAg and/or HDAg polypeptides. Methods are performed largely as described in Antony Chen, Gustaf Ahlen, Erwin D. Brenndorfer, Anette Brass, Fredrik Holmstrom, Margaret Chen, Jonas Soderholm, David R. Milich, Lars Frelin and Matti Sallberg (2011) Heterologous T Cells Can Help Restore Function in Dysfunctional Hepatitis C Virus Nonstructural 3/4A- Specific T Cells during Therapeutic Vaccination. J Immunol 186:5107-5118, the contents of which are hereby incorporated by reference in their entirety as to the entire disclosure of pages 5107 through 51 18 inclusive. In sum, the immunogenicity of the constructs tested are evaluated after introducing the constructs into animals using the IVTN injector with electroporation (see PCT/IB2012/001321 (WO 2012/172424 Al, published December 20, 2012), hereby expressly incorporated by reference in its entirety. After administration of the various constructs to the animals, with or without additional boosts, the immunogenicity of the constructs are evaluated (e.g., T helper and CTL-speeific immune responses, cytokine responses, and/or antibody responses are evaluated and the efficacy of the various constructs tested are compared). It will be determined that the construct comprising the codon-optimized sequence encoding e.g., HDAg gt 1 A B, HDag gt 2 A B, HDAg-L or HDAg-S sequence or both will be more immunogenic (e.g., stronger T helper and CTL-specific immune responses, cytokine responses, and/or antibody responses) than the construct encoding wild-type i.e. HDAg gt 1 A/B, HDag gt 2 A/B, HDAg-L or HDAg-S sequence or both. It will also be determined that the construct encoding a fusion of HBcAg (e.g., a nucleic acid encoding an avian HBcAg that has been codon optimized for expression in humans) when administered with a construct comprising i.e. HDAg gt I A/B, HDag gt 2 A/B, HDAg-L or HDAg-S sequence or both will be more immunogenic (e.g., stronger T helper and CTL-specific immune responses, cytokine responses, and/or antibody responses).

Administration Regimen

[0084] Truncated Therapeutic administration of a preventative therapy for HBV and HDV persons of risk is performed in patients with or without an existing HBV infection. Some patients who receive a booster dose start treatment within 1-2 months after the booster dose. Treatment begins after a mean interval of 15 months (range 1-30) from last administration.

[0085] Patients are preferably HDV treatment naive. Patients receive administrations of an HDV-containing immunogenic composition (e.g., one or more of the contracts depicted in FIGURE 2 and/or 3 in the deltoid muscles (e.g., four monthly administrations with 167 _ug, 500 μg, or 1.500 μ§ codon-optimized HDV immunogen formulations delivered by in vivo electroporation (EP) in some approaches). Enrollment may be done with two weeks interval between patients for safety reasons. It is expected that the administration will significantly improve IFNy producing responses to HDAg during the first six weeks of therapy. Patients are expected to experience 0.61ogl0 - 2.41ogl 0 reduction in serum HDV RNA and some are expected to be effectively treated (e.g., HDV viral titer is reduced) or cured (e.g., HDV viral titer is reduced to undetectable amounts by a clinical assay).

[0086] Patients are administered the therapy and in one minute or less electroporation is performed, for example as described in PCT Publication No. WO 2012/172424 Al , published December 20, 2012, which is hereby incorporated by reference in its entirety not only as it relates to electroporation but for all content disclosed therein.

[0087] By some approaches, a volume of 0.5 mL 0.9% sodium chloride containing the DNA is injected in the deltoid muscle (alternating left and right) using an IVTN needle at a depth of 1.2 cm. The injection site is marked prior to injection with a surgical pen and then sterilized by swiping with an alcohol pad. Immediately after the injection or along with the injection an IVIN-based electroporator is used at the site of injection and electroporation is administered, as described, for example, in PCT Publication No. WO 2012/172424 Al, published December 20, 2012, incorporated by rreeffeerreennccee iinn iittss eennttiirreettyy hheerree aanndd aabboovvee.. TThhee aaddmmiinniissttrraattiioonn iiss eexxppeecctteedd t too bbee ssaaffee aanndd wweellll t toolleerraatteedd bbyy rreecciippiieennttss..

[[00008888]] PPaattiieennttss wwiillll ddeemmoonnssttrraattee aann iinnccrreeaassee iinn rreellaattiivvee aannttiibbooddyy lleevveellss ddeetteecctteedd bbyy aa ppaaiirreedd ccoommppaarriissoonn ooff tthhee ssaammpplleess oobbttaaiinneedd aatt wweeeekk 00 aanndd 22,, aann eeffffeecctt,, wwhhiicchh iiss mmoosstt pprroonnoouunncceedd iinn tthhee ttwwoo lloowweesstt ddoossee ggrroouuppss.. SSoommee ppaattiieennttss wwiillll ddeemmoonnssttrraattee ddee nnoovvoo TT cceellll aaccttiivvaattiioonn.. TThhee pprreesseennccee ooff H HBBVV aanndd//oorr HHDDVV ssppeecciifificc TT cceellll rreessppoonnsseess bbeeffoorree,, dduurriinngg aanndd aafftteerr tthhee tthheerraappeeuuttiicc aaddmmiinniissttrraattiioonn iiss ddeetteerrmmiinneedd aass tthhee nnuummbbeerr ooff IIFFNNyy --pprroodduucciinngg TT cceellllss,, oorr ssppoott ffoorrmmiinngg cceellllss ((SSFFCCss)) bbyy EELLIISSppoott,, aanndd tthhee lleevveell ooff pprroolliiffeerraattiioonn aass ddeetteerrmmiinneedd bbyy tthhee lleevveell ooff [[33]]HH--tthhyymmiiddiinnee iinnccoorrppoorraattiioonn.. IInn tthhee EELLIISSppoott aassssaayy,, oonnllyy tthhee rreessppoonnsseess ttoo nniinnee ppeeppttiiddee ppoooollss ssppaannnniinngg tthhee wwhhoollee HHDDAAgg rreeggiioonn aarree uusseedd ffoorr tthhee ssttaattiissttiiccaall ccoommppaarriissoonn ttoo aavvooiidd rreeppeeaatteedd uussee ooff tthhee ssaammee eeppiittooppee aanndd ttoo oovveerrccoommee U HLLAA--rreessttrriiccttiioonn.. IInn ssoommee aalltteerraannttiivveess,, tthhee EELLIISSppoott aassssaayy iiss ppeerrffoorrmmeedd ttoo aassssaayy ffoorr tthhee rreellaattiivvee aannttiibbooddyy lleevveellss oorr tthhee pprreesseennccee ooff HHBBVV aanndd//oorr HHDDVV ssppeecciifificc TT cceellll rreessppoonnsseess bbeeffoorree,, dduurriinngg aanndd aafftteerr tthhee tthheerraappeeuuttiicc aaddmmiinniissttrraattiioonn.. TThhee pprreesseennccee ooff HHDDAAgg--ssppeecciifificc TT cceellllss ccaann bbee ddeetteecctteedd bbyy EELLIISSppoott uussiinngg rreeccoommbbiinnaanntt HHDDAAGG oorr ppeeppttiiddeess tthhaatt ccaann ssppaann tthhee ccoommpplleettee HHDDaagg ccoorrrreessppoonnddiinngg ttoo HHDDVV ggeennoottyyppeess 11 oorr 22.. IInn ssoommee aalltteerrnnaattiivveess,, tthhee ppeeppttiiddeess ccoommppririssee tthhee aammiinnoo aacciidd sseeqquueenncceess sseett ffoorr iinn aannyy oonnee ooff SSEEQQ IIDD NNOO''ss :: 7755--111166..

[[00008899]] TThhee nnuummbbeerr ooff tthhee IIFFNNyy --pprroodduucciinngg ssppoottss aarree eexxppeecctteedd ttoo iinnccrreeaassee aafftteerr tthhee ttwwoo fifirrsstt vvaacccciinnaattiioonnss wwhheenn ccoommppaarriinngg tthhee nnuummbbeerr ooff SSFFCCss aatt wweeeekk 00,, aanndd tthhee ssaammee aatt wweeeekkss 22 aanndd 66.. PPrroolliiffeerraattiivvee TT cceellll rreessppoonnsseess ttoo H HDDAAgg aarree ddeetteecctteedd iinn aa ssuubbssttaannttiiaall nnuummbbeerr ooff ssuubbjjeeccttss pprriioorr ttoo oorr aafftteerr vvaacccciinnaattiioonn,, ddee nnoovvoo EELLIISSppoott rreessppoonnsseess aarree oobbsseerrvveedd iinn aa ffrraaccttiioonn ooff aallll ggrroouuppss oobbsseerrvveedd.. IInn ssoommee ppaattiieennttss tthhee aaccttiivvaattiioonn,, oorr rreeaaccttiivvaattiioonn,, ooff HHDDVV HHDDAAgg IIFFNNyy --pprroodduucciinngg TT c ceellllss ccooiinncciiddeess wwiitthh tthhee ssuupppprreessssiioonn ooff tthhee HHDDVV R RNNAA lleevveellss iinn bblloooodd..

[[00009900]] AA rraappiidd vviirraall rreessppoonnssee,, aanndd ccoommpplleettee eeaarrllyy vviirraall rreessppoonnssee aanndd ssuussttaaiinneedd vviirraall rreessppoonnssee wwiillll bbee sseeeenn iinn aa ssuubbssttaannttiiaall nnuummbbeerr ooff ppaattiieennttss..

[0091] The Enzyme-linked immunospot (ELISpot) assay is used to determine immune responses. Without being limiting, this can include monitoring cell mediated immunity as this technique is sensitive and can be accurate for the detection of rare antigen specific T cells or B ceils. This can be performed after an initial immunization or after a booster after the initial immunization, for example. [[00009922]] IInn aann EELLIISSPPOOTT aassssaayy,, tthhee ssuurrffaacceess iinn tthhee wweellllss ooff mmiiccrroottiitteerr ppllaattee aarree ccooaatteedd wwiitthh aa ccaappttuurree aannttiibbooddyy tthhaatt bbiinnddss aa ssppeecciifificc eeppiittooppee ooff aa pprrootteeiinn tthhaatt iiss bbeeiinngg aassssaayyeedd.. DDuurriinngg tthhee cceellll iinnccuubbaattiioonn aanndd ssttiimmuullaattiioonn sstteepp,, PPBBMMCCss aarree sseeeeddeedd iinnttoo tthhee wweellllss ooff tthhee ppllaattee aalloonngg wwiitthh tthhee aannttiiggeenn,, aanndd ffoorrmm aa mmoonnoollaayyeerr oonn tthhee mmeemmbbrraannee ssuurrffaaccee ooff tthhee wweellll.. AAss tthhee aannttiiggeenn--ssppeecciifificc cceellllss aarree aaccttiivvaatteedd,, tthheeyy rreelleeaassee tthhee ccyyttookkiinnee,, wwhhiicchh iiss ccaappttuurreedd ddiirreeccttllyy oonn tthhee mmeemmbbrraannee ssuurrffaaccee bbyy tthhee iimmmmoobbiilliizzeedd aannttiibbooddyy.. IInn tthhee aalltteerrnnaattiivveess hheerreeiinn,, tthhee EELLIISSppoott iiss uusseedd ttoo ddeetteerrmmiinnee aa ssppeecciifificc pprrootteeiinn uussiinngg PPBBMMCCss tthhaatt aarree iissoollaatteedd ffrroomm tthhee mmiiccee.. TThhee t teecchhnniiqquueess ffoorr tthhee EELLIISSppoott aarree ddeessccriribbeedd iinn AAhhlleenn eett aall.

22001166 ((iinnccoorrppoorraatteedd bbyy rreeffeerreennccee hheerreeiinn)).. IInn ssoommee aalltteerrnnaattiivveess,,

IImmmmuunniizzaattiioonn wwiitthh aa nnuucclleeiicc aacciidd

[[00009933]] IImmmmuunniizzaattiioonn ccaann bbee ppeerrffoorrmmeedd wwiitthh aa nnuucclleeiicc aacciidd,, ssuucchh aass R RNNAA oorr

DDNNAA,, ffoorr eexxaammppllee.. AAnn aapppprrooaacchh ooff rreepprroodduucciibbiiyy ddeelliivveerriinngg ggeenneettiicc mmaatteerriiaall iinn mmuussccllee ttiissssuuee iinn iiss bbyy hhyyddrrooddyynnaammiicc iinnjjeeccttiioonn,, wwhhiicchh iiss aa ffoorrcceedd iinnjjeeccttiioonn ooff aa vvoolluummee eeqquuaalliinngg tthhee vvoolluummee ooff tthhee ttiissssuuee ttoo bbee ttrraannssffeecctteedd tthheerreebbyy ccaauussiinngg aann iinnccrreeaasseedd llooccaall pprreessssuurree rreessuullttiinngg iinn aann iimmpprroovveedd uuppttaakkee ooff ggeenneettiicc mmaatteerriiaall.. IInn ssoommee aalltteerrnnaattiivveess,, aa ssmmaallll iinnjjeeccttiioonn vvoolluummee ccaann bbee ddeelliivveerreedd ttoo aa ttaarrggeetteedd ttiissssuuee vvoolluummee,, tteerrmmeedd iinn vviivvoo iinnttrraacceelllluullaarr iinnjjeeccttiioonn

((IIVVINN)).. IInn ssoommee aalltteerrnnaattiivveess,, aa ddeevviiccee bbaasseedd oonn nneeeeddllee((ss)) wwiitthh a appeerrttuurreess aalloonngg tthhee nneeeeddllee sshhaaffttss,, wwhheerree mmuullttiippllee nneeeeddlleess ccaann fifixx tthhee ttiissssuuee vvoolluummee ttoo bbee ttrraannssffeecctteedd,, iiss uusseedd ffoorr iimmmmuunniizzaattiioonn wwiitthh aa nnuucclleeiicc aacciidd.. IInn ssoommee aalltteerrnnaattiivveess,, iimmmmuunniizzaattiioonn iiss ppeerrffoorrmmeedd wwiitthh iinn vviivvoo eelleeccttrrooppoorraattiioonn.. TThhee tteecchhnniiqquuee ooff uussiinngg IIVVTTNN iiss ddeessccrriibbeedd iinn AAhhlleenn eett aall.. 22001166

((iinnccoorrppoorraatteedd bbyy rreeffeerreennccee iinn iittss eennttiirreettyy)).. AAddddiittiioonnaall nnuucclleeiicc aacciidd ddeelliivveerr}}'' ddeevviicceess wwiitthh aanndd wwiitthhoouutt eelleeccttrrooppoorraattiioonn aarree aallssoo ccoonntteemmppllaatteedd ffoorr uussee iinn ddeelliivveerriinngg aannyy oonnee oorr mmoorree ooff tthhee ccoonnssttrruuccttss ddeessccrriibbeedd hheerreeiinn iinncclluuddiinngg,, wwiitthhoouutt lliimmiittaattiioonn,, tthhee MMeeddppuullssaarr®®,, ee..gg..,, aass ddeessccriribbeedd iinn U USS PPaatteenntt NNoo.. 66,,774488,,226655,, UUSS PPaatteenntt NNoo.. 66,,774466,,444411 ,, aanndd UUSS PPaatteenntt N Noo..

66,,776633,,226644;; tthhee IIGGEEAA ddeevviiccee,, ee..gg..,, aass ddeessccriribbeedd iinn U USS PPaatteenntt NNoo.. 99331144662211 ,, oorr tthhee IICCHHOORR ddeevviiccee,, aass ddeessccriribbeedd iinn UUSS PPaatteenntt NNoo,, 66227788889955,, aallll ooff wwhhggiicchh aarree hheerreebbyy eexxpprreessssllyy iinnccoorrppoorraatteedd bbyy rreeffeerreennccee iinn tthheeiirr eennttiirreettiieess.,

[[00009944]] I IVVTTNN ddeelliivveerryy hhaass bbeeeenn sshhoowwnn ttoo iimmpprroovvee tthhee iimmmmuunnooggeenniicciittyy aanndd ccaann bbee mmoorree eeffffeeccttiivvee wwiitthh iinn vviivvoo eelleeccttrroottrraannssffeerr..

Animals for the testing of the HDV vaccination

[0095] Groups of 5 mice were immunized with 50 ₍ ug of DNA using in vivo electroporation as described (Ahlen et al., 2016; incorporated by reference in its entirety). In brief, mice were immunized with 50 μΐ of saline containing 50 μg of DNA in the tibialis anterior muscle, immediately after immunization, the site was treated with in vivo el ectr operation as described (Ahlen et al., 2016; incorporated by reference in its entirety). Half of the mice were sacrificed after 2 weeks, whereas the other half was boosted exactly the same way at 4 weeks, and then sacrificed two weeks later. Spleens were harvested and the presence of HDAg-specific T cells was detected by ELISpot as described (Ahlen et al., 2016) using recombinant HDAg or peptides spanning the complete HDAg corresponding to HDV genotypes 1 and 2 (see Table 1).

[0096] Results. The ELISpot assays showed that 2 weeks after a single immunization HDV specific T cells were primed using the HDV constructs 1-5, and 7-10 towards gtl peptides (Figures 4A-4T)(Table 1; peptides). At two weeks after a booster dose at 4 week the HDV DNA constructs 1-5 and 8-10 primed the HDV specific T cells. Thus, unexpectedly, most constructs were immunogenic in vivo and could therefore potentially be used in humans. As shown below is the sequences that were used that are shown in Figures 4A-T and 5A-5T (Table 1).

L-HDAg~gt2~#7 2 KDKDGEGAPPAKRARTDQME 102 2

L-HDAg-gi2-#8 2 AKRARTDQ EVDSGPRKRKH 103 2

L-HDAg-gt2-#9 2 VDSGPRKRKHPGGFTEQERR 104 2

L-HDAg-gt2-#10 2 PGGFTEQERRDHRRRKALEN 105 2

L-HDAg-gt2-#1 1 2 DHRRRKALENKKKQLSSGGK 106 3

L-HDAg-gi2-#12 2 KKKQLSSGGKDLSREEEEEL 107 3

L-HDAg-gt2-#13 2 DLSREEEEELRRLTEEDERR 108 3

L-HDAg-gi2-#14 2 RRLTEEDERRERRVAGPRVG 109 3

L-HDAg-gt2-#15 2 ERRVAGPRVGDVNPLDGGPR 1 10 3

L-HDAg-gt2-#16 2 DVNPLDGGPRGAPGGGFVPS 1 1 1 4

L-HDAg-gi2-#17 2 GAPGGGFVPS QG!PESPFT 1 12 4

L-HDAg-gt2-#18 2 QG!PESPFTRRGDGLDTRG 1 13 4

L-HDAg-gi2-#19 2 RRGDGLDTRGTQEFPWVNPQ 1 14 4

L-HDAg-gt2-#20 2 TQEFPWVNPQPPPPRLPLLE 1 15 4

L-HDAg-gt2-#21 2 PPPPRLPLLECTPQ 1 16 4

[0097] Table I : Peptide pool design. A total of twenty-one 20-mer peptides (each having 10 amino acid (aa) overlap) covering the full-length HDV large antigen of genotype 1 and 2 were purchased from Sigma Aldrich (St. Louis, MO). The twenty-one peptides were divided into four peptide pools as outlined in the table.

[0098] For Figure 5, there were ten constructs tested at both two weeks and then 6 weeks.

⁾ ] Expression of the chimeric protein was tested via Western blot using a PreS l antibody and the anti-HDV antibody,

sits:

[0100] As shown in Figure 6, all constructs expressed the expected proteins and with the expected antigenicity. The PreSl antibody only detected the Δ1 , Δ2, Δ3, Δ4, Δ7 and Δ8 expression products as these were the only ones with preS I sequences (Figure 6A). The HDAg-specific antibody detected expression products of the expected sizes from all constructs (Figure 6B). The data also shows that the P2A cleavage is very- effective as only the cleaved products are detected (Figure 6). Thus, all HDV containing plasmids are functional,

[0101] As shown in Figure 6A the rows have in order the vector, marker, Δ1, Δ2, Δ3, Δ4, Δ6, marker, marker, Δ7, Δ8, Δ9, Δ10. As shown in Figure 6B the rows have in order the vector, marker, Δ1 , Δ2, Δ3, Δ4, Δ6, marker, marker, Δ7, Δ8, Δ9, Δ10.

al

Delta 1 wild type constructs can be manufactured with a DNA sequence comprising a sequence set forth in SEQ ID NO: 1 1 , which also comprises restriction sites (Hindlll/ EcoRI). In some alternatives, the delta 1 construct is optimized for expression in humans and comprises a sequence set forth in SEQ ID NO: 13 (Delta 1 optimized with restriction sites (Hindlll and EcoRI).

[0103] Delta 2 wild type constructs can be manufactured with a DNA sequence comprising a sequence set forth in SEQ ID NO: 16, which also comprises restriction sites (Hindlll/ EcoRI). In some alternatives, the Delta 2 construct is optimized for expression in humans and comprises a sequence set forth in SEQ ID NO: 17 or 18 (Delta 2 optimized with restriction sites (Hindlll and EcoRI). In some alternatives, the Delta 2 protein comprises a sequence set forth in SEQ ID NO: 19.

[0104] Delta 3 wild type constructs can be manufactured with a DNA sequence comprising a sequence set forth in SEQ ID NO: 20 or 21 (with restriction sites Hindlll and EcoRI). In some alternatives, the Delta 3 construct is optimized for expression in humans and comprises a sequence set forth in SEQ ID NO: 22 or 23 (Delta

3 codon optimized with restriction sites (Hindlll and EcoRI). In some alternatives, the Delta 3 protein comprises a sequence set forth in SEQ ID NO: 24.

[0105] Delta 4 wild type constructs can be manufactured with a DNA sequence comprising a sequence set forth in SEQ ID NO: 25 or 26 (with restriction sites Hindlll and EcoRI). In some alternatives, the Delta 4 construct is codon optimized for expression in humans and comprises a sequence set forth in SEQ ID NO: 27 or 28 (Delta

4 optimized with restriction sites (Hindlll and EcoRI). In some alternatives, the Delta 4 protein comprises a sequence set forth in SEQ ID NO: 29.

[0106] Delta 5 wild type constructs can be manufactured with a DNA sequence comprising a sequence set forth in SEQ ID NO: 30 or 31 (with restriction sites Hindlll and EcoRI). In some alternatives, the Delta 5 construct is codon optimized for expression in humans and comprises a sequence set forth in SEQ ID NO: 32 or 33 (Delta

5 optimized with restriction sites (Hindlll and EcoRI). In some alternatives, the Delta 5 protein comprises a sequence set forth in SEQ ID NO: 34.

[0107] Delta 6 wild type constructs can be manufactured with a DNA sequence comprising a sequence set forth in SEQ ID NO: 35 or 36 (with restriction sites Hindfll and EcoRI ). In some alternatives, the Delta 6 construct is codon optimized for expression in humans and comprises a sequence set forth in SEQ ID NO: 37 or 38 (Delta

6 optimized with restriction sites (Hindlll and EcoRI). In some alternatives, the Delta 6 protein comprises a sequence set forth in SEQ ID NO: 39. [0108] Delta 7 wild type constructs can be manufactured with a DNA sequence comprising a sequence set forth in SEQ ID NO: 40 or 41 (with restriction sites HindHI and EcoRl). In some alternatives, the Delta 7 construct is codon optimized for expression in humans and comprises a sequence set forth in SEQ ID NO: 42 or 43 (Delta

7 optimized with restriction sites (HindHI and EcoRl). In some alternatives, the Delta 7 protein comprises a sequence set forth in SEQ ID NO: 44.

[0109] Delta 8 wild type constructs can be manufactured with a DNA sequence comprising a sequence set forth in SEQ ID NO: 45 or 46 (with restriction sites HindHI and EcoRl). In some alternatives, the Delta 8 construct is codon optimized for expression in humans and comprises a sequence set forth in SEQ ID NO: 47 or 48 (Delta

8 optimized with restriction sites (HindHI and EcoRl). In some alternatives, the Delta 8 protein comprises a sequence set forth in SEQ ID NO: 49.

[0110] Delta 9 wild type constructs can be manufactured with a DNA sequence comprising a sequence set forth in SEQ ID NO: 50 or 51 (with restriction sites HindHI and EcoRl). In some alternatives, the Delta 9 construct is codon optimized for expression in humans and comprises a sequence set forth in SEQ ID NO: 52 or 53 (Delta

9 optimized with restriction sites (HindHI and EcoRl). In some alternatives, the Delta 9 protein comprises a sequence set forth in SEQ ID NO: 54.

[0111] Delta 10 wild type constructs can be manufactured with a DNA sequence comprising a sequence set forth in SEQ ID NO: 55 or 56 (with restriction sites HindHI and EcoRl). In some alternatives, the Delta 10 constmct is codon optimized for expression in humans and comprises a sequence set forth in SEQ ID NO: 57 or 58 (Delta

10 optimized with restriction sites (HindHI and EcoRl). In some alternatives, the Delta 10 protein comprises a sequence set forth in SEQ ID NO: 59.

[0112] Core I wild type constructs can be manufactured with a DNA sequence comprising a sequence set forth in SEQ ID NO: 60 or 61 (with restriction sites HindHI and EcoRl). In some alternatives, the Core 1 construct is codon optimized for expression in humans and comprises a sequence set forth in SEQ ID NO: 62 or 63 (Core 1 optimized with restriction sites (HindHI and EcoRT). In some alternatives, the Core 1 protein comprises a sequence set forth in SEQ ID NO: 64.

[0113] Pre-C-gt-H wild type constructs can be manufactured with a DNA sequence comprising a sequence set forth in SEQ ID NO: 65 or 66 (with restriction sites HindHI and EcoRl). In some alternatives, the Pre-C-gt-H constmct is codon optimized for expression in humans and comprises a sequence set forth in SEQ ID NO: 67 or 68 (Pre- C-gt-H optimized with restriction sites (Hindlll and EcoRI) for cloning purposes). In some alternatives, the Pre-C-gt-H protein comprises a sequence set forth in SEQ ID NO: 69.

[0114] PreC-C-Mut-gt-H wild type constructs can be manufactured with a DNA sequence comprising a sequence set forth in SEQ ID NO: 70 or 71 (with restriction sites Hindlll and EcoRI ). In some alternatives, the PreC-C-Mut-gt-H construct is codon optimized for expression in humans and comprises a sequence set forth in SEQ ID NO: 72 or 73 (PreC-C-Mut-gt-H optimized with restriction sites (Hindlll and EcoRI) for cloning puiposes). In some alternatives, the PreC-C-Mut-gt-H protein comprises a sequence set forth in SEQ ID NO: 74.

[0115] In some alternatives, a chimeric gene comprising Core sequences is provided. In some alternatives, the chimeric gene further comprises HDAg sequences. In some alternatives, a protein encoded by the chimeric gene is provided. In some alternatives, a composition is provided, wherein the composition comprises the chimeric gene. In some alternatives, a composition is provided, wherein the composition comprises the protein.

[0116] In some alternatives, a chimeric gene comprising HDAg sequences is provided. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preSl derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HDAg genotype I B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2A (P2A), foot-and-mouth disease virus (FMDV) 2A (F2A), equine rhinitis A vims (ERAV) 2A (E2A) and Thosea asigna virus 2A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine-serine-glycine) motif at an N-terminus. In some alternatives, the at least one preSl derived sequence is preSl A and/or preSl B. In some alternatives, the at least one preSl derived sequence is preSl A and comprises an amino acid sequence set forth in SEQ ID NO: I . In some alternatives, the at least one preSl derived sequence is preSl B and comprises an amino acid sequence set forth in SEQ ID NO: 2, In some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4. In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, preS l B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 10 or 12, In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 15 or 17, In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 20 or 22, In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 25 or 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's: 30 or 32. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ) ID NO:'s 35 or 37. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 40 or 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 45 or 47, In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50 or 52, In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 55 or 57. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59. In some alternatives, the chimeric gene further comprises sequences encoding HBV Core. In some alternatives, the sequences encoding the HBV Core comprises a sequence set forth in SEQ ID NO: 60 or 62.

[0117] In some alternatives, the HBV Core comprises an amino acid sequence set forth in SEQ ID NO: 64. In some alternatives, the chimeric gene further comprises sequences encoding Pre-C-gt-H. In some alternatives, the sequences encoding the Pre-C- gt-H comprise a sequence set forth in SEQ ID NO: 65 or 67. In some alternatives, the Pre- C-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 69. In some alternatives, the chimeric gene further comprises sequences encoding PreC-C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt-H comprise a sequence set forth in SEQ ID NO: 70 or 72. In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 74. In some alternatives, the chimeric gene is codon optimized for expression in humans.

[0118] In some alternatives, a chimeric protein comprising at least two HDAg protein domains, encoded by the chimeric gene of anyone of the alternatives described herein is provided. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preSl derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HDAg genotype 1 B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2A (P2A), foot-and-mouth disease virus (FMDV) 2A (F2A), equine rhinitis A virus (ERAV) 2A (E2A) and Thosea asigna virus 2A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine-serine-glycine) motif at an N-terminus. In some alternatives, the at least one preSl derived sequence is preSl A and/or preSl B. In some alternatives, the at least one preS l derived sequence is preS l A and comprises an amino acid sequence set forth in SEQ ID NO: 1 . In some alternatives, the at least one preSl derived sequence is preSl B and comprises an amino acid sequence set forth in SEQ ID NO: 2, In some alternatives, the sequence encoding HDAg genotype I A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4. In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, pre SI B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 10 or 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 15 or 17. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 20 or 22. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 25 or 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ) ID NO's: 30 or 32. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 35 or 37. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 40 or 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 45 or 47, In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50 or 52. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 55 or 57. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ) ID NO: 59 In some alternatives, the chimeric gene further comprises sequences encoding HBV Core, In some alternatives, the sequences encoding the HBV Core comprises a sequence set forth in SEQ ID NO: 60 or 62. In some alternatives, the HBV Core comprises an amino acid sequence set forth in SEQ ID NO: 64. In some alternatives, the chimeric gene further comprises sequences encoding Pre-C- gt-H. In some alternatives, the sequences encoding the Pre-C-gt-H comprise a sequence set forth in SEQ ID NO: 65 or 67. In some alternatives, the Pre-C-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 69. In some alternatives, the chimeric gene further comprises sequences encoding PreC-C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt-H comprise a sequence set forth in SEQ ID NO: 70 or 72. In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 74. In some alternatives, the chimeric gene is codon optimized for expression in humans.

[0119] In some alternatives, a composition comprising anyone or more of the chimeric genes of any one of the alternatives is provided. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preSl derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HDAg genotype 1 B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2A (P2A), foot-and-mouth disease vims FMDV) 2A (F2A), equine rhinitis A vims (ERAV) 2A (E2A) and Thosea asigna virus 2 A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine- serine-glycine) motif at an N-terminus. In some alternatives, the at least one preSl derived sequence is preS l A and/or preSl B, In some alternatives, the at least one preSl derived sequence is preS l A and comprises an amino acid sequence set forth in SEQ ID NO: 1. In some alternatives, the at least one preSl derived sequence is preS l B and comprises an amino acid sequence set forth in SEQ ID NO: 2. In some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4, In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5, In some alternatives, preSl B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ) ID NO's 10 or 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 15 or 17. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 20 or 22. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 25 or 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's: 30 or 32. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 35 or 37. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 40 or 42. In some alteraatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 45 or 47. In some alteraatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50 or 52. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 55 or 57. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59. In some alternatives, the chimeric gene further comprises sequences encoding HBV Core. In some alternatives, the sequences encoding the HBV Core comprises a sequence set forth in SEQ ID NO: 60 or 62. In some alternatives, the HBV Core comprises an amino acid sequence set forth in SEQ ID NO: 64. In some alternatives, the chimeric gene further comprises sequences encoding Pre-C-gt-H. In some alternatives, the sequences encoding the Pre-C-gt-H comprise a sequence set forth in SEQ ID NO: 65 or 67. In some alternatives, the Pre-C-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 69. In some alternatives, the chimeric gene further comprises sequences encoding PreC-C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt-H comprise a sequence set forth in SEQ ID NO: 70 or 72. In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 74. In some alternatives, the chimeric gene is codon optimized for expression in humans, In some alternatives, the composition further comprises the chimeric protein of anyone of the alternatives herein. In some alternatives, the chimeric protein is encoded by any one of the chimeric genes provided herein. In some alternatives, the composition further comprises an adjuvant. In some alternatives, said adjuvant comprises a nucleic acid encoding a polypeptide adjuvant. In some alternatives, said polypeptide adjuvant is IL-12, IL-15, or IL-21. In some alteraatives, said adjuvant is ribavirin or a CpG- containing nucleic acid. In some alternatives, said adjuvant is a polypeptide. In some alternatives, said adjuvant comprises an adjuvant promoting portion or subunit of IL-12, IL-15, o IL-21 , [0120] In some alternatives, the chimeric gene or composition of any one of the alternatives is for use in generating an immune response in a subject or for DNA vaccination so as to inhibit, ameliorate, treat, or prevent HBV and/or HDV infection. In some alternatives, the composition comprises anyone or more of the chimeric genes of any one of the alternatives described herein. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preSl derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HDAg genotype 1 B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2A (P2A), foot-and-mouth disease virus (FMDV) 2A (F2A), equine rhinitis A virus (ERAV) 2A (E2A) and Thosea asigna virus 2 A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine- serine-glycine) motif at an -terminus. In some alternatives, the at least one preSl derived sequence is preS l A and/or preSl B. In some alternatives, the at least one preSl derived sequence is preS l A and comprises an amino acid sequence set forth in SEQ ID NO: 1. In some alternatives, the at least one preSl derived sequence is preS l B and comprises an amino acid sequence set forth in SEQ ID NO: 2. In some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4, In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5, In some alternatives, pre SI B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ) ID NO's 10 or 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 15 or 17. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 20 or 22. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 25 or 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's: 30 or 32. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 35 or 37. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 40 or 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 45 or 47. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50 or 52. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ) ID NO:'s 55 or 57. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59. In some alternatives, the chimeric gene further comprises sequences encoding HBV Core. In some alternatives, the sequences encoding the HBV Core comprises a sequence set forth in SEQ ID NO: 60 or 62. In some alternatives, the HBV Core comprises an amino acid sequence set forth in SEQ ID NO: 64. In some alternatives, the chimeric gene further comprises sequences encoding Pre-C-gt-H. In some alternatives, the sequences encoding the Pre-C-gt-H comprise a sequence set forth in SEQ ID NO: 65 or 67. In some alternatives, the Pre-C-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 69. In some alternatives, the chimeric gene further comprises sequences encoding PreC-C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt-H comprise a sequence set forth in SEQ ID NO: 70 or 72. In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 74. In some alternatives, the chimeric gene is codon optimized for expression in humans. In some alternatives, the composition further comprises the chimeric protein of anyone of the alternatives herein. In some alternatives, the chimeric protein is encoded by any one of the chimeric genes provided herein. In some alternatives, the composition further comprises an adjuvant. In some alternatives, said adjuvant comprises a nucleic acid encoding a polypeptide adjuvant. In some alternatives, said polypeptide adjuvant is IL-12, IL-15, or IL-21. In some alternatives, said adjuvant is ribavirin or a CpG- containing nucleic acid. In some alternatives, said adjuvant is a polypeptide. In some alternatives, said adjuvant comprises an adjuvant promoting portion or subunit of IL-12, IL-15, or IL-21.

[0121] In some alternatives, the chimeric gene or composition of any one of the alternatives herein, is for use in generating an antibody, T-lymphocyte or CTL-specific response in a subject so as to inhibit, ameliorate, treat, or prevent an HBV and/or HDV infection. In some alternatives, the composition comprises anyone or more of the chimeric genes of any one of the alternatives described herein. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one pre SI derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HDAg genotype 1 B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2 A (P2A), foot-and-mouth disease virus (FMDV) 2 A (F2A), equine rhinitis A virus (ERAV) 2 A (E2A) and Thosea asigna virus 2A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine- serine-glycine) motif at an N-terminus. In some alternatives, the at least one preSl derived sequence is preSl A and/or preSl B, In some alternatives, the at least one preSl derived sequence is preS l A and comprises an amino acid sequence set forth in SEQ) ID NO: I . In some alternatives, the at least one preSl derived sequence is preS l B and comprises an amino acid sequence set forth in SEQ ID NO: 2, in some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4. In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, preSl B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 10 or 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 15 or 17. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 20 or 22, In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 25 or 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's: 30 or 32. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 35 or 37. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 40 or 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 45 or 47. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ED NO: 49. En some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50 or 52. En some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 's 55 or 57. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59. In some alternatives, the chimeric gene further comprises sequences encoding HBV Core. In some alternatives, the sequences encoding the HBV Core comprises a sequence set forth in SEQ ID NO: 60 or 62, In some alternatives, the HBV Core comprises an amino acid sequence set forth in SEQ ID NO: 64, In some alternatives, the chimeric gene further comprises sequences encoding Pre-C-gt-H. In some alternatives, the sequences encoding the Pre-C-gt-H comprise a sequence set forth in SEQ ID NO: 65 or 67, In some alternatives, the Pre-C-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 69. In some alternatives, the chimeric gene further comprises sequences encoding PreC-C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt-H comprise a sequence set forth in SEQ ED NO: 70 or 72, In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEsQ ID NO: 74, In some alternatives, the chimeric gene is codon optimized for expression in humans. In some alternatives, the composition further comprises the chimeric protein of anyone of the alternatives herein. In some alternatives, the chimeric protein is encoded by any one of the chimeric genes provided herein. In some alternatives, the composition further comprises an adjuvant. In some alternatives, said adjuvant comprises a nucleic acid encoding a polypeptide adjuvant. In some alternatives, said polypeptide adjuvant is IL-12, IL-1 5, or EL-21. In some alternatives, said adjuvant is ribavirin or a CpG- containing nucleic acid. In some alternatives, said adjuvant is a polypeptide. En some alternatives, said adj uvant compri ses an adjuvant promoting portion or subunit of IL-12, IL-15, or IL-21.

[0122] In some alternatives, the chimeric gene or composition of any one of the alternatives described herein is for DNA vaccination or to induce an immunogenic response against HBV and/or HDV in a subject that has been identified as having and HDV and/or HBV infection. En some alternatives, the composition comprises anyone or more of the chimeric genes of any one of the alternatives described herein. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preSI derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype I A, HDAg genotype 1 B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2A (P2A), foot- and-mouth disease virus (FMDV) 2A (F2A), equine rhinitis A virus (ERAV) 2A (E2A) and Thosea asigna virus 2A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine-serine-glycine) motif at an N-terminus. In some alternatives, the at least one preSI derived sequence is pre SI A and/or preSI B. In some alternatives, the at least one preS I derived sequence is preS I A and comprises an amino acid sequence set forth in SEQ ID NO: 1. In some alternatives, the at least one preS I derived sequence is pre SI B and comprises an amino acid sequence set forth in SEQ ID NO: 2. In some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4, In some alternatives, pre SI A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, preS I B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 10 or 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 15 or 17. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 20 or 22, In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 25 or 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's: 30 or 32. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 35 or 37. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 40 or 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 45 or 47. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50 or 52, In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 55 or 57. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59. In some alternatives, the chimeric gene further comprises sequences encoding HBV Core. In some alternatives, the sequences encoding the HBV Core comprises a sequence set forth in SEQ ID NO: 60 or 62. In some alternatives, the HBV Core comprises an amino acid sequence set forth in SEQ ID NO: 64, In some alternatives, the chimeric gene further comprises sequences encoding Pre-C- gt-H. In some alternatives, the sequences encoding the Pre-C-gt-H comprise a sequence set forth in SEQ ID NO: 65 or 67. In some alternatives, the Pre-C-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 69. In some alternatives, the chimeric gene further comprises sequences encoding PreC-C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt-H comprise a sequence set forth in SEQ ID NO: 70 or 72. In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 74. In some alternatives, the chimeric gene is codon optimized for expression in humans. In some alternatives, the composition further comprises the chimeric protein of anyone of the alternatives herein. In some alternatives, the chimeric protein is encoded by any one of the chimeric genes provided herein. In some alternatives, the composition further comprises an adjuvant. In some alternatives, said adjuvant comprises a nucleic acid encoding a polypeptide adjuvant. In some alternatives, said polypeptide adjuvant is IL-12, IL-15, or IL-21. In some alternatives, said adjuvant is ribavirin or a CpG- containing nucleic acid. In some alternatives, said adjuvant is a polypeptide. In some alternatives, said adjuvant comprises an adjuvant promoting portion or sub unit of IL-12, IL-15, or IL-21.

[0123] In some alternatives, a method of eliciting an immune response is provided, wherein the method comprises administering to a subject having HDV infection and/or HBV infection the nucleic acid or composition of any one of the alternatives herein. In some alternatives, the composition comprises anyone or more of the chimeric genes of any one of the alternatives described herein. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preSl derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HDAg genotype I B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2A (P2A), foot-and-mouth disease virus (FMDV) 2A (F2A), equine rhinitis A virus (ERAV) 2A (E2A) and Thosea asigna virus 2A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine- serine-glycine) motif at an N-temiinus. In some alternatives, the at least one preSl derived sequence is preSl A and/or preS l B. In some alternatives, the at least one preSl derived sequence is preSl A and comprises an amino acid sequence set forth in SEQ ID NO: 1. In some alternatives, the at least one preSl derived sequence is preSl B and comprises an amino acid sequence set forth in SEQ ID NO: 2. In some alternatives, the sequence encoding HDAg genotype 1 A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4. In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, pre SI B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. in some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 10 or 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14, In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 15 or 17. in some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 20 or 22. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 25 or 27. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's: 30 or 32. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 35 or 37. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 40 or 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 45 or 47. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50 or 52. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 55 or 57, In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59. In some alternatives, the chimeric gene further comprises sequences encoding HBV Core. In some alternatives, the sequences encoding the HBV Core comprises a sequence set forth in SEQ ID NO: 60 or 62. In some alternatives, the HBV Core comprises an amino acid sequence set forth in SEQ ID NO: 64. In some alternatives, the chimeric gene further comprises sequences encoding Pre-C-gt-H. In some alternatives, the sequences encoding the Pre-C-gt-H comprise a sequence set forth in SEQ ID NO: 65 or 67. In some alternatives, the Pre-C-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 69, In some alternatives, the chimeric gene further comprises sequences encoding PreC-C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt~H comprise a sequence set forth in SEQ ID NO: 70 or 72. In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 74. In some alternatives, the chimeric gene is codon optimized for expression in humans. In some alternatives, the composition further comprises the chimeric protein of anyone of the alternatives herein. In some alternatives, the chimeric protein is encoded by any one of the chimeric genes provided herein. In some alternatives, the composition further comprises an adjuvant. In some alternatives, said adjuvant comprises a nucleic acid encoding a polypeptide adjuvant. In some alternatives, said polypeptide adjuvant is IL-12, IL-15, or IL-21. In some alternatives, said adjuvant is ribavirin or a CpG- containing nucleic acid. In some alternatives, said adjuvant is a polypeptide. In some alternatives, said adjuvant comprises an adjuvant promoting portion or subunit of IL-12, IL-15, or IL-21. In some alternatives, said administering comprises injecting said nucleic acid into a patient, such as using an ΓνΊΝ needle, Medpulsar®, or ICHOR device with or without electroporation. In some alternatives, the method further comprising administering a second administration of a nucleic acid or composition of any one of the alternatives described herein. In some alternatives, the method further comprises providing an adjuvant. In some alternatives, said adjuvant is a nucleic acid encoding a polypeptide adjuvant, such as IL-12, IL-15, or IL-21. In some alternatives, said adjuvant is IL-12, IL-15, or IL-21. In some alternatives, said second administration is given after said first time. In some alternatives, said adjuvant is given before, during, or after administration of said nucleic acid or composition of any one of claims 1-45. In some alternatives, said second administration is given one week, two weeks, three weeks, four weeks, five weeks, or six weeks after the first administration of said nucleic acid or composition of any one of claims 1-45. In some alternatives, the subject has been identified as a person at risk of contracting HDV or that has HDV. In some alternatives, the method further comprises evaluating the subject for an immunoresponse after administering the compositions of anyone of the alternatives here. In some alternatives, the evaluating is performed by an ELISpot assay. In some alternatives, the ELISpot assay is performed using any one of the peptides comprising a sequence set forth in SEQ ID NO: 75-1 16.

[0124] In some alternatives, a method of increasing preSl antibodies in a subject in need, the method comprising administering the compositions of anyone of the alternatives described herein to the subject in need. In some alternatives, the composition comprises anyone or more of the chimeric genes of any one of the alternatives described herein. The chimeric gene can have at least two sequences encoding hepatitis D antigen (HDAg), at least one cleavage sequence and at least one preSl derived sequence. In some alternatives, the at least two sequences comprise a full or partial HDAg gene. In some alternatives, the at least two sequences encoding HDAg comprises a sequence encoding HDAg genotype 1 A, HD Ag genotype 1 B, HDAg genotype 2 A and/or HDAg genotype 2 B. In some alternatives, the at least two sequences encoding hepatitis D antigen (HDAg) are joined by the at least one cleavage sequence. In some alternatives, the at least one cleavage sequence is selected from the group consisting of porcine teschovirus-1 2A (P2A), foot-and-mouth disease vims (FMDV) 2A (F2A), equine rhinitis A virus (ERAV) 2A (E2A) and Thosea asigna virus 2A (T2A), wherein each cleavage sequence can be modified to include a GSG (glycine-serine-glycine) motif at an N-terminus. In some alternatives, the at least one preSl derived sequence is preSl A and/or preSl B. In some alternatives, the at least one pre SI derived sequence is preSl A and comprises an amino acid sequence set forth in SEQ ID NO: 1. In some alternatives, the at least one preS l derived sequence is pre SI B and comprises an amino acid sequence set forth in SEQ ID NO: 2. In some alternatives, the sequence encoding HDAg genotype I A comprises a nucleic acid sequence set forth in SEQ ID NO: 3. In some alternatives, the sequence encoding HDAg genotype 1 B comprises a nucleic acid sequence set forth in SEQ ID NO: 4. In some alternatives, preSl A is encoded by a nucleic acid sequence set forth in SEQ ID NO: 5. In some alternatives, preSl B is encoded by a nucleic acid sequence set forth in SEQ ID NO: 6. In some alternatives, the at least one cleavage sequence is a T2 A sequence and is encoded by a nucleic acid sequence set forth in SEQ ID NO: 7. In some alternatives, the at least two sequences comprises a sequence encoding HDAg genotype 2 A and comprises a sequence set forth in SEQ ID NO: 8. In some alternatives, the at least- two sequences comprises a sequence encoding HDAg genotype 2 B and comprises a sequence set forth in SEQ ID NO: 9. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 10 or 12. In some alternatives, the chimeric gene encodes a protein comprises an amino acid sequence set forth in SEQ ID NO: 14. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 15 or 17. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 19. in some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's 20 or 22. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 24. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 25 or 27. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 29. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO's: 30 or 32, In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 34. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 35 or 37. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 39. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 40 or 42. In some alternatives, the chimeric gene encodes a protein wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 44. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 45 or 47. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 49. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO: 50 or 52. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 54. In some alternatives, the chimeric gene comprises a nucleic acid sequence set forth in SEQ ID NO:'s 55 or 57. In some alternatives, the chimeric gene encodes a protein, wherein the protein comprises an amino acid sequence set forth in SEQ ID NO: 59, In some alternatives, the chimeric gene further comprises sequences encoding HBV Core. In some alternatives, the sequences encoding the HBV Core comprises a sequence set forth in SEQ ID NO: 60 or 62, In some alternatives, the HBV Core comprises an amino acid sequence set forth in SEQ ID NO: 64. In some alternatives, the chimeric gene further comprises sequences encoding Pre-C- gt-H. In some alternatives, the sequences encoding the Pre-C-gt-H comprises a sequence set forth in SEQ ID NO: 65 or 67. In some alternatives, the Pre-C-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 69. In some alternatives, the chimeric gene further comprises sequences encoding PreC-C-Mut-gt-H. In some alternatives, the sequences encoding the PreC-C-Mut-gt-H comprises a sequence set forth in SEQ ID NO: 70 or 72. In some alternatives, the PreC-C-Mut-gt-H comprises an amino acid sequence set forth in SEQ ID NO: 74. In some alternatives, the chimeric gene is eodon optimized for expression in humans. In some alternatives, the composition further comprises the chimeric protein of anyone of the alternatives herein. In some alternatives, the chimeric protein is encoded by any one of the chimeric genes provided herein. In some alternatives, the composition further comprises an adjuvant. In some alternatives, said adjuvant comprises a nucleic acid encoding a polypeptide adjuvant. In some alternatives, said polypeptide adjuvant is IL-12, IL-15, or IL-21. In some alternatives, said adjuvant is ribavirin or a CpG-containing nucleic acid. In some alternatives, said adjuvant is a polypeptide. In some alternatives, said adjuvant comprises an adjuvant promoting portion or subunit of IL-12, IL-15, or IL-21. In some alternatives, the method further comprises evaluating the subject for an immunoresponse after administering the compositions of anyone of the alternatives here. In some alternatives, the evaluating is performed by an ELISpot assay. In some alternatives, the ELISpot assay is performed using any one of the peptides comprising a sequence set forth in SEQ ID NO: 75-116.

[0125] The term "comprising" as used herein is synonymous with "including," "containing," or "characterized by," and is inclusive or open-ended and does not exclude additional, unrecited elements or method steps,

[0126] All numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification are to be understood as being modified in all instances by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth herein are approximations that may vary depending upon the desired properties sought to be obtained. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of any claims in any application claiming priority to the present application, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding approaches.

[0127] The above description discloses several methods and materials of the present invention. This invention is susceptible to modifications in the methods and materials, as well as alterations in the fabrication methods and equipment. Such modifications will become apparent to those skilled in the art from a consideration of this disclosure or practice of the invention disclosed herein. Consequently, it is not intended that this invention be limited to the specific alternatives disclosed herein, but that it cover all modifications and alternatives coming within the true scope and spirit of the invention.

[0128] All references cited herein, including but not limited to published and unpublished applications, patents, and literature references, are incorporated herein by reference in their entirety and are hereby made a part of this specification. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and/or take precedence over any such contradictor}' material. Aspects of the invention may also include one or more of the following sequences, alone or in combination or a sequence encoding one or more of the peptide sequences provided:

SEQ ID NO: 1 Pre SI A

GTNLSTSNPLGFFPDHQLDPAFRANSANPDWDFNPNKDTWPDANKVG

SEQ ID NO: 2 PreSl B

GQNLSTSNPLGFFPDHQLDPAFRANTANPDWDFNPNKDTWPDANKVG

SEQ ID NO: 3 HDAg genotype 1 A

AGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCGCGAAGAAATTCTGGAA

CAGTGGGTGGGCGCGCGCAAAAAACTGGAAGAACTGGAACGCGATCTGCGC

AAAATTAAAAAAAAAATTAAAAAACTGGAAGAAGAAAACCCGTGGCTGGGC

AACATTAAAGGCATTCTGGGCAAAAAAGATCGCGAAGGCGAAGGCGCGCCG

CCGGCGAAACGCGCGCGCGCGGATCAGATGGAAGTGGATAGCGGCCCGCGC

AAACGCCCGTTTCGCGGCGAATTTACCGATAAAGAACGCCGCGATCATCGCC

GCCGCAAAGCGCTGGAAAACAAACGCAAACAGCTGAGCAGCGGCGGCAAAA

GCCTGAGCAAAGAAGAAGAAGAAGAACTGCGCAAACTGACCGAAGAAGATG

AACGCCGCGAACGCCGCGTGGCGGGCCCGCGCGTGGGCGGCGTGAACCCGCT

GGAAGGCGGCACCCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAG

GGCGTGCCGGAAAGCCCGTTTGCGCGCACCGGCGAAGGCCTGGATGTGCGCG GCAACCAGGGCTTTCCGTGGGATATTCTGTTTCCGGCGGATCCGCCGTTTAGC

CCGCAGAGCTGCCGCCCGCAG

SEQ ID NO: 4 HDAg genotype J B nucleic acid

AGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCGCGAAGAAGTGCTGGAA

CAGTGGGTGAACGGCCGCAAAAAACTGGAAGAACTGGAACGCGAACTGCGC

CGCGCGCGCAAAAAAATTAAAAAACTGGAAGATGATAACCCGTGGCTGGGC

A AC GT G A A AGGC A T TC TGGGC A A A A A AG AT A A AG ATGGC G A AGGC GC GC C G

CCGGCGAAACGCGCGCGCACCGATCAGATGGAAATTGATAGCGGCCCGCGCA

AACGCCCGCTGCGCGGCGGCTTTACCGATCGCGAACGCCAGGATCATCGCCG

CCGCAAAGCGCTGAAAAACAAAAAAAAACAGCTGAGCGCGGGCGGCAAAAG

CCTGAGCAAAGAAGAAGAAGAAGAACTGAAACGCCTGACCCGCGAAGATGA

AGAACGCAAAAAAGAAGAACATGGCCCGAGCCGCCTGGGCGTGAACCCGAG

CGAAGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAG

GGCATTCCGGAAAGCCGCTTTACCCGCACCGGCGAAGGCCTGGATGTGCGCG

GCAGCCGCGGCTTTCCGCAGGATATTCTGTTTCCGAGCGATCCGCCGTTTAGC

CCGCAGAGCTGCCGCCCGCAG

SEQ ID NO: 5 pre S I derived sequence is pre SI

GGCACCAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCT

GGATCCGGCGTTTCGCGCGAACAGCGCGAACCCGGATTGGGATTTTAACCCG

AACAAAGATACCTGGCCGGATGCGAACAAAGTGGGC

SEQ ID NO: 6 preSl B

GGCCAGAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCT GGATCCGGCGTTTCGCGCGAACACCGCGAACCCGGATTGGGATTTTAACCCG

AACAAAGATACCTGGCCGGATGCGAACAAAGTGGGC

SEQ ID NO: T2A nucleic acid

GGAAGCGGAGCTACTAACTTCAGCCTGCTGAAGCAGGCTGGAGACGTGGAGG AGAACCCTGGACCT

SEQ ID NO: 8 HDAg gentotype 2 A (wt)

ATGAGCCAGAGCGAAACCCGCCGCGGCCGCCGCGGCACCCGCGAAGAAACC CTGGAAAAATGGATTACCGCGCGCAAAAAAGCGGAAGAACTGGAAAAAGAT CTGCGCAAAACCCGCAAAACCATTAAAAAACTGGAAGAAGAAAACCCGTGG

CTGGGCAACATTGTGGGCATTATTCGCAAAGGCAAAGATGGCGAAGGCGCGC

CGCCGGCGAAACGCCCGCGCACCGATCAGATGGAAGTGGATAGCGGCCCGG

GCAAACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACGCGAAGATCATCG

CCGCCGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAGCGCGGGCGGCAA

AATTCTGAGCAAAGAAGAAGAAGAAGAACTGCGCCGCCTGACCGATGAAGA

TGAAGAACGCAAACGCCGCGTGGCGGGCCCGCGCGTGGGCGATGTGAACCCG

AGCCGCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGCAGATGG

CGGGCGTGCCGGAAAGCCCGTTTAGCCGCACCGGCGAAGGCCTGGATATTCG

CGGCACCCAGGGCTTTCCGTGGGTGAGCCCGAGCCCGCCGCAGCAGCGCCTG

CCGCTGCTGGAATGCACCCCGCAG

SEQ ID NO: 9 HDAg gentotype 2 B (wt)

AGCCAGAGCGAAAGCAAAAAAAACCGCCGCGGCGGCCGCGAAGATATTCTG

GAAAAATGGATTACCACCCGCCGCAAAGCGGAAGAACTGGAAAAAGATCTG

CGCAAAGCGCGCAAAACCATTAAAAAACTGGAAGATGAAAACCCGTGGCTG

GGCAACATTATTGGCATTATTCGCAAAGGCAAAGATGGCGAAGGCGCGCCGC

CGGCGAAACGCCCGCGCACCGATCAGATGGAAATTGATAGCGGCACCGGCAA

ACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACGCGAAGATCATCGCCGC

CGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAGCAGCGGCGGCAAAAAC

CTGAGCCGCGAAGAAGAAGAAGAACTGGGCCGCCTGACCGTGGAAGATGAA

GAACGCCGCCGCCGCGTGGCGGGCCCGCGCACCGGCGATGTGAACCTGAGCG

GCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGCGCATGGAAGG

CGTGCCGGAAAGCCCGTTTACCCGCACCGGCGAAGGCCTGGATATTCGCGGC

AACCAGGGCTTTCCGTGGGTGCGCCCGAGCCCGCCGCAGCAGCGCCTGCCGC

TGCTGGAATGCACCCCGCAG

SEO ID NO: 10 delta 1 wt

AGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCGCGAAGAAATTCTGGAA

C AGTGGGTGGGC GC GC GC A AA AA AC TGGA AGAAC TGGAAC GC GATC TGC GC

AAAATTAAAAAAAAAATTAAAAAACTGGAAGAAGAAAACCCGTGGCTGGGC

AACATTAAAGGCATTCTGGGCAAAAAAGATCGCGAAGGCGAAGGCGCGCCG

CCGGCGAAACGCGCGCGCGCGGATCAGATGGAAGTGGATAGCGGCCCGCGC

AAACGCCCGTTTCGCGGCGAATTTACCGATAAAGAACGCCGCGATCATCGCC

GCCGCAAAGCGCTGGAAAACAAACGCAAACAGCTGAGCAGCGGCGGCAAAA

GCCTGAGCAAAGAAGAAGAAGAAGAACTGCGCAAACTGACCGAAGAAGATG

AACGCCGCGAACGCCGCGTGGCGGGCCCGCGCGTGGGCGGCGTGAACCCGCT

GGAAGGCGGCACCCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAG

GGCGTGCCGGAAAGCCCGTTTGCGCGCACCGGCGAAGGCCTGGATGTGCGCG

GCAACCAGGGCTTTCCGTGGGATATTCTGTTTCCGGCGGATCCGCCGTTTAGC

CCGCAGAGCTGCCGCCCGCAGAGCCGCAGCGAAAGCAAAAAAAACCGCGGC

GGCCGCGAAGAAGTGCTGGAACAGTGGGTGAACGGCCGCAAAAAACTGGAA

GAACTGGAACGCGAACTGCGCCGCGCGCGCAAAAAAATTAAAAAACTGGAA

GATGATAACCCGTGGCTGGGCAACGTGAAAGGCATTCTGGGCAAAAAAGATA

AAGATGGCGAAGGCGCGCCGCCGGCGAAACGCGCGCGCACCGATCAGATGG

AAATTGATAGCGGCCCGCGCAAACGCCCGCTGCGCGGCGGCTTTACCGATCG

CGAACGCCAGGATCATCGCCGCCGCAAAGCGCTGAAAAACAAAAAAAAACA

GCTGAGCGCGGGCGGCAAAAGCCTGAGCAAAGAAGAAGAAGAAGAACTGAA

ACGCCTGACCCGCGAAGATGAAGAACGCAAAAAAGAAGAACATGGCCCGAG CCGCCTGGGCGTGAACCCGAGCGAAGGCGGCCCGCGCGGCGCGCCGGGCGG CGGCTTTGTGCCGAGCATGCAGGGCATTCCGGAAAGCCGCTTTACCCGCACC

GGCGAAGGCCTGGATGTGCGCGGCAGCCGCGGCTTTCCGCAGGATATTCTGT

TTCCGAGCGATCCGCCGTTTAGCCCGCAGAGCTGCCGCCCGCAGGGCACCAA

CCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGG

CGTTTCGCGCGAACAGCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGA

TACCTGGCCGGATGCGAACAAAGTGGGCGGCCAGAACCTGAGCACCAGCAAC

CCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACAC

CGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCG

AACAAAGTGGGCGGAAGCGGAGCTACTAACTTCAGCCTGCTGAAGCAGGCTG

GAGACGTGGAGGAGAACCCTGGACCTATGAGCCAGAGCGAAACCCGCCGCG

GCCGCCGCGGCACCCGCGAAGAAACCCTGGAAAAATGGATTACCGCGCGCAA

AAAAGCGGAAGAACTGGAAAAAGATCTGCGCAAAACCCGCAAAACCATTAA

AAAACTGGAAGAAGAAAACCCGTGGCTGGGCAACATTGTGGGCATTATTCGC

AAAGGCAAAGATGGCGAAGGCGCGCCGCCGGCGAAACGCCCGCGCACCGAT

CAGATGGAAGTGGATAGCGGCCCGGGCAAACGCCCGCATAAAAGCGGCTTTA

CCGATAAAGAACGCGAAGATCATCGCCGCCGCAAAGCGCTGGAAAACAAAA

AAAAACAGCTGAGCGCGGGCGGCAAAATTCTGAGCAAAGAAGAAGAAGAAG

AACTGCGCCGCCTGACCGATGAAGATGAAGAACGCAAACGCCGCGTGGCGG

GCCCGCGCGTGGGCGATGTGAACCCGAGCCGCGGCGGCCCGCGCGGCGCGCC

GGGCGGCGGCTTTGTGCCGCAGATGGCGGGCGTGCCGGAAAGCCCGTTTAGC

CGCACCGGCGAAGGCCTGGATATTCGCGGCACCCAGGGCTTTCCGTGGGTGA

GCCCGAGCCCGCCGCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCGCAGAG

CCAGAGCGAAAGCAAAAAAAACCGCCGCGGCGGCCGCGAAGATATTCTGGA

AAAATGGATTACCACCCGCCGCAAAGCGGAAGAACTGGAAAAAGATCTGCG

CAAAGCGCGCAAAACCATTAAAAAACTGGAAGATGAAAACCCGTGGCTGGG

CAACATTATTGGCATTATTCGCAAAGGCAAAGATGGCGAAGGCGCGCCGCCG

GCGAAACGCCCGCGCACCGATCAGATGGAAATTGATAGCGGCACCGGCAAAC

GCCCGCATAAAAGCGGCTTTACCGATAAAGAACGCGAAGATCATCGCCGCCG

CAAAGCGCTGGAAAACAAAAAAAAACAGCTGAGCAGCGGCGGC AAAAACCT

GAGCCGCGAAGAAGAAGAAGAACTGGGCCGCCTGACCGTGGAAGATGAAGA

ACGCCGCCGCCGCGTGGCGGGCCCGCGCACCGGCGATGTGAACCTGAGCGGC

GGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGCGCATGGAAGGCG

TGCCGGAAAGCCCGTTTACCCGCACCGGCGAAGGCCTGGATATTCGCGGCAA

CCAGGGCTTTCCGTGGGTGCGCCCGAGCCCGCCGCAGCAGCGCCTGCCGCTG

CTGGAATGCACCCCGCAGGGCACCAACCTGAGCACCAGCAACCCGCTGGGCT

TTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACAGCGCGAACCCG

GATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGG

GCGGCCAGAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCA

GCTGGATCCGGCGTTTCGCGCGAACACCGCGAACCCGGATTGGGATTTTAAC

CCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGGC

SEQ ID NO: 11 deltal wt with restriction sites (Hindffl/ EcoRI)

A AGCTTG CCATGGCCAGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGC

CGCGAAGAAATTCTGGAACAGTGGGTGGGCGCGCGCAAAAAACTGGAAGAA

CTGGAACGCGATCTGCGCAAAATTAAAAAAAAAATTAAAAAACTGGAAGAA

GAAAACCCGTGGCTGGGCAACATTAAAGGCATTCTGGGCAAAAAAGATCGCG

AAGGCGAAGGCGCGCCGCCGGCGAAACGCGCGCGCGCGGATCAGATGGAAG

TGGATAGCGGCCCGCGCAAACGCCCGTTTCGCGGCGAATTTACCGATAAAGA ACGCCGCGATCATCGCCGCCGCAAAGCGCTGGAAAACAAACGCAAACAGCTG

AGCAGCGGCGGCAAAAGCCTGAGCAAAGAAGAAGAAGAAGAACTGCGCAAA

CTGACCGAAGAAGATGAACGCCGCGAACGCCGCGTGGCGGGCCCGCGCGTG

GGCGGCGTGAACCCGCTGGAAGGCGGCACCCGCGGCGCGCCGGGCGGCGGC

TTTGTGCCGAGCATGCAGGGCGTGCCGGAAAGCCCGTTTGCGCGCACCGGCG

AAGGCCTGGATGTGCGCGGCAACCAGGGCTTTCCGTGGGATATTCTGTTTCCG

GCGGATCCGCCGTTTAGCCCGCAGAGCTGCCGCCCGCAGAGCCGCAGCGAAA

GC A A A A A A A AC CGC GGC GGC CGC G A AG A AGTGC TG G A AC AGTGGGTGA AC G

GCCGCAAAAAACTGGAAGAACTGGAACGCGAACTGCGCCGCGCGCGCAAAA

AAATTAAAAAACTGGAAGATGATAACCCGTGGCTGGGCAACGTGAAAGGCAT

TCTGGGCAAAAAAGATAAAGATGGCGAAGGCGCGCCGCCGGCGAAACGCGC

GCGCACCGATCAGATGGAAATTGATAGCGGCCCGCGCAAACGCCCGCTGCGC

GGCGGCTTTACCGATCGCGAACGCCAGGATCATCGCCGCCGCAAAGCGCTGA

AAAACAAAAAAAAACAGCTGAGCGCGGGCGGCAAAAGCCTGAGCAAAGAAG

AAGAAGAAGAACTGAAACGCCTGACCCGCGAAGATGAAGAACGCAAAAAAG

AAGAACATGGCCCGAGCCGCCTGGGCGTGAACCCGAGCGAAGGCGGCCCGC

GCGGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAGGGCATTCCGGAAAG

CCGCTTTACCCGCACCGGCGAAGGCCTGGATGTGCGCGGCAGCCGCGGCTTT

CCGCAGGATATTCTGTTTCCGAGCGATCCGCCGTTTAGCCCGCAGAGCTGCCG

CCCGCAGGGCACCAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGAT

CATCAGCTGGATCCGGCGTTTCGCGCGAACAGCGCGAACCCGGATTGGGATT

TTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCGGCCAGA

ACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCG

GCGTTTCGCGCGAACACCGCGAACCCGGATTGGGATTTTAACCCGAACAAAG

ATACCTGGCCGGATGCGAACAAAGTGGGCGGAAGCGGAGCTACTAACTTCAG

CCTGCTGAAGCAGGCTGGAGACGTGGAGGAGAACCCTGGACCTATGAGCCA

GAGCGAAACCCGCCGCGGCCGCCGCGGCACCCGCGAAGAAACCCTGGAAAA

ATGGATTACCGCGCGCAAAAAAGCGGAAGAACTGGAAAAAGATCTGCGCAA

AACCCGCAAAACCATTAAAAAACTGGAAGAAGAAAACCCGTGGCTGGGCAA

CATTGTGGGCATTATTCGCAAAGGCAAAGATGGCGAAGGCGCGCCGCCGGCG

AAACGCCCGCGCACCGATCAGATGGAAGTGGATAGCGGCCCGGGCAAACGC

CCGCATAAAAGCGGCTTTACCGATAAAGAACGCGAAGATCATCGCCGCCGCA

AAGCGCTGGAAAACAAAAAAAAACAGCTGAGCGCGGGCGGCAAAATTCTGA

GCAAAGAAGAAGAAGAAGAACTGCGCCGCCTGACCGATGAAGATGAAGAAC

GCAAACGCCGCGTGGCGGGCCCGCGCGTGGGCGATGTGAACCCGAGCCGCGG

CGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGCAGATGGCGGGCGTG

CCGGAAAGCCCGTTTAGCCGCACCGGCGAAGGCCTGGATATTCGCGGCACCC

AGGGCTTTCCGTGGGTGAGCCCGAGCCCGCCGCAGCAGCGCCTGCCGCTGCT

GGAATGCACCCCGCAGAGCCAGAGCGAAAGCAAAAAAAACCGCCGCGGCGG

CCGCGAAGATATTCTGGAAAAATGGATTACCACCCGCCGCAAAGCGGAAGAA

CTGGAAAAAGATCTGCGCAAAGCGCGCAAAACCATTAAAAAACTGGAAGAT

GAAAACCCGTGGCTGGGCAACATTATTGGCATTATTCGCAAAGGCAAAGATG

GCGAAGGCGCGCCGCCGGCGAAACGCCCGCGCACCGATCAGATGGAAATTG

ATAGCGGCACCGGCAAACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACG

CGAAGATCATCGCCGCCGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAG

CAGCGGCGGCAAAAACCTGAGCCGCGAAGAAGAAGAAGAACTGGGCCGCCT

GAC C GTGG A AGATGAAG A ACGC C GC C GC C GC GTGGCGGGC C CGC GC AC CGG

CGATGTGAACCTGAGCGGCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTT

GTGCCGCGCATGGAAGGCGTGCCGGAAAGCCCGTTTACCCGCACCGGCGAAG GCCTGGATATTCGCGGCAACCAGGGCTTTCCGTGGGTGCGCCCGAGCCCGCC

GCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCGCAGGGCACCAACCTGAGC

ACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCG

CGCGAACAGCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATACCTGG

CCGGATGCGAACAAAGTGGGCGGCCAGAACCTGAGCACCAGCAACCCGCTG

GGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACACCGCGAA

CCCGGATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAA

GTGGGCTGATGAG AATTCCGT

SEQ ID NO: 12 codon optimized delta 1

G C C AG C AG AAG GAA C AAAAAAG ΑΆΤ C G G G GAG G G C G G G AAGAAAT C C T G GAAC AG T G G G T C G GAG C AC G GAAGAAAC T G GAAGAAC G GAGAG G GAC C G C G C AAGAT C AAGAAGAAG AT C AG AAG C T G GAG GAG G AGAAC C C C T G G C T G G G C AA T AT C AAG G G CAT C C G G G C AAG AAG GAT C G G GAG G GAGAG G GAG C AC C AC C T G C AAAG AG G G C C AG G C C GAC C AGAT G GAG G T G GAT AG C G GAC C AAG GAAG C G C C C T T T C AGAG GAGAG T T TAG C GAC AAG GAG C G GAGA GATCACAGGCGCCGGAAGGCCC TGGAGAACAAGAGGAAGCAGCTGAGCTCCGGCGGCAAG T C C C T G T C T AAG GAG GAG GAG GAG GAG C T G C G C AAG C T GAC AGAG GAG GAC GAGAGAAG G GAGAG GAG G G T G G C AG GAC C TAG G G T G G GAG G C G T GAAC C C AC T G GAG G GAG G AAC C AGA G GAG C AC C T G GAG GAG GA T T C G T G C C AT C CAT G C AG G GAG T G C C C GAG TCTCCT T T TGCC C G GAC AG G C GAG G G C C T G GAT G T GAGAG G C AAT C AG G G CT TCCCCTGG GAC AT C C T G T T T C C T G C C G A T C C A C C C T T C T C T C C T C AG A G C T G C C G G C C AC AGAG C AG A T C C GAG T C AG AA GAAC AG G G GAG G AAGAGAG GAG G T G C T G GAG C AG T G G G T GAAT G G C C G GAAG AAG C T G GAG GAG C T G GAG C G G GAG C T GAG AAG G G C C AGAAAGAAG AT C AAGAAG C T G GAAG AC GAT AAT C C T T G G C T G G G C A AT G T G AA G G C A T C C T G G G C A AG A AG G A C AG GAT G GAGA G G G A G C AC C T C C AG C AAAGAG G G C AAGAAC C GAC C AGAT G GAGAT C GAT T C T G GAC C AAG GAAG C G C C C C C T GAGAG GAG G C T T C AC AGAC C G G GAGAG AC AG GAT C AC C G C C G G AGAAAG G C C C T GAAG A A C AAG AAG AG C A G C T G T C C G C C G G G G C AAG A G C C T G T C C AAAG AAG A G G A A GAG GAG C T GAAG AG G C T GAC C C G C GAG GAC GAG GAGAG GAAG AAG GAG GAG C AC G GAC C A AG C AG G C T G G GAG T GAAT C C T T C C G A G G G A G GAC C TAG G G G A G C AC C AG G G G A G G C T T C G T G C CAT C T AT G C AG G G CAT C C C C GAGAG C C G G T T C C AGAAC G G GAG G G C C T G GAC G T GAG G G G C T C C C G C G G C T T T C C T C AG GAC AT C C T G T T C C CA C T GAT C C C C C T T T T T C C C C C C AG T C T T G TAG G C C T C AG G G C AC C AAC C T G T C T AC AG C AA C C AC T G G G C T T C T T T C C C GAC C AC C AG C T G GzAT CCTGCCT TCCGCGC C AAC AG C G C C AAT C C C GAC T G G GAC T T C AAC C C AAA AAG GAC AC C T G G C C AG A G C C AAC AAG G T C G G C G G C C AGAAC C T G T C C AC A T C T AAT CCTCTGGGCT TCT T TC C AG A C C AC C AG C T G G T C C G C C T T C C G G G C C AAC A C A G C T AAC C C T GAC T G G GAC T T C AAC C C C AAT AAG GAT AC T T G G C C C GAC G C C AAC AAG G T C GGCGGAAGCGGAGCTACTAACT CAGCC GCTGAAGCAGGCTGGAGACGTGGAGGAGAAC C C T G G C C T T GAG C C AG T C C G G AC AAG G G G G G C C G GAG G G A A C C AG G GAG GAG C A C T G GAGAAG T G GAT C AC AG C C C G C AAG AAG G C C GAG GAG C T G G AGAAG GAC C T G C G GAAG ACCAGAAAGACAATCAAGAAGCTGGAAGAAGAGAACCCATGGCTGGGCAATATCGTGGGC AT CAT C AGAAAG G G C AAG GAC G G C GAG G GAG C AC C AC C AG C AAAGAG G C C C AG GAC T GAT C AG A G GAAG T C GA AG C G GAC C AG G C AAG C G G C C T C AC AAG T C C G G C T T C AC AG AC AAG GAGA GAGAG GAC CAT AG G C G C C G GAAG G C C C T G GAAAAC AAGAAGAAG C AAT TAT C C G C C G G C G G C AAGAT C C T G T C C AAAGAG GAAGAAGAG GAG C T GAGAAG G C T GAC C GAC GAG GAT G A G GAG G G A . AA.G AAG G G T G G C AG G C C AAG G G T G G G C GAC G T GAAT C C C AG C AG G G G A G GAC C AAG G GCGCCCCTGGCGGCGGCT TCG G C C A C AG A T G G C G G A G T G C C AG A GAG C C C C T T T T C C AG GAC AG GAGAG G G C C T G GAT AT C AGAG G C AC C C AG G G C T T T C C T T G G G T G TC TCCAAGCCCTCCACAGCAGCGGCTGCCACTGC TGGAGTGCACCCCTCAGTCCCAGTCT GAGAG CAAGAAGAAC AGAAG G G G C G G C AGAGAG GAC AT C C T G GAGAAG T G GAT C AC C AC A C G C AG AAAAG C T GAAGAAC T G GAAAAG GAC C T GAG GAAG G C C C G C AAAAC AAT C AAG AAG C T G GAG GAT GAAAAT CCAT GGC T GGGAAACAT CAT CGGCAT CAT C A G G A A G G G C AAG G C G G G GAAG G C G C AC C AC C T G C AAAG C G G C C T AGAAC AGAT C AGAT G GAAAT C GAT T C T G G C AC C G G C AAGAG G C C AC AC AAGAG C G G C T T C AC C GAC AAG GAG C G C GAG GA T C AC AGAAG G C

GCAAGGCCCTGGAGAACAAGAAGAAGCAAT TAAGCAGCGGCGGCAAGAATCTGTCCAGAG AAGAAGAGGAGGAGCTGGGCCGCCTGACCGTGGAGGACGAGGAGCGGAGAAGGCGCGTGG C AG GAC C AC G C AC AG G C GAT G T G AAC C T G T C C G GAG GAG GAC C AAG G G GAG C AC C T G GAG G C G G C T T C G T G C C TAG A AT G GAG G GAG T G C C T GAG T C C C C C T T C AC C C G C AC C G G A GAG G G C C T G GAC AT C AGAG G C ΑΑΤ C AG G GAT T C C CAT G G G T GAG G C C C AG C C C AC C AC AG C AG C G C C T G C C AC T G C T G GAG T G TAG C C C C C AG G G C AC AAAC C T G T C C AC C T C T AA C C C C T G G GCT TCT T TCC GAT C A T C AG C T G GAC C C AG C C T T C AG G G C C AAC T C C G C C AA T C C AGAT T G G GAC T T C AAC C C GAAT AAG GAT AC T T G G C C AGAT G C AAAC AAG G T C G GAG GAC AGAAC C T GAG C A CAT C C AC C C T C T G G G C T T C T T T C C T G A C CAT C AG C T G G A T C C C G C C T T T C G C G C C AA T AC C G C C AAC C C T GAT T G G GAC T T C AAC C C T AAT AAG GAT AC T T G G C C T GAT G C T A ATAAGGTCGGG

SEQ ID NO: 13 : Delta 1 optimized with restriction sites (HindlH and EcoRI)

A AGCTTGC/ CCATGGCCAGCAGAAGTGAATCAAAAAAGAATCGGGGAGGG

CGGGAAGAAATCCTGGAACAGTGGGTCGGAGCACGGAAGAAACTGGAAGAA

CTGGAGAGGGACCTGCGCAAGATCAAGAAGAAGATCAAGAAGCTGGAGGAG

GAGAACCCCTGGCTGGGCAATATCAAGGGCATCCTGGGCAAGAAGGATCGGG

AGGGAGAGGGAGCACCACCTGCAAAGAGGGCCAGAGCCGACCAGATGGAGG

TGGATAGCGGACCAAGGAAGCGCCCTTTCAGAGGAGAGTTTACCGACAAGGA

GCGGAGAGATCACAGGCGCCGGAAGGCCCTGGAGAACAAGAGGAAGCAGCT

GAGCTCCGGCGGCAAGTCCCTGTCTAAGGAGGAGGAGGAGGAGCTGCGCAA

GCTGACAGAGGAGGACGAGAGAAGGGAGAGGAGGGTGGCAGGACCTAGGGT

GGGAGGCGTGAACCCACTGGAGGGAGGAACCAGAGGAGCACCTGGAGGAGG

ATTCGTGCCATCCATGCAGGGAGTGCCCGAGTCTCCTTTTGCCCGGACAGGCG

AGGGCCTGGATGTGAGAGGCAATCAGGGCTTCCCCTGGGACATCCTGTTTCCT

GCCGATCCACCCTTCTCTCCTCAGAGCTGCCGGCCACAGAGCAGATCCGAGTC

TAAGAAGAACAGGGGAGGAAGAGAGGAGGTGCTGGAGCAGTGGGTGAATGG

CCGGAAGAAGCTGGAGGAGCTGGAGCGGGAGCTGAGAAGGGCCAGAAAGAA

GATCAAGAAGCTGGAAGACGATAATCCTTGGCTGGGCAATGTGAAAGGCATC

CTGGGCAAGAAGGACAAGGATGGAGAGGGAGCACCTCCAGCAAAGAGGGCA

AGAACCGACCAGATGGAGATCGATTCTGGACCAAGGAAGCGCCCCCTGAGAG

GAGGCTTCACAGACCGGGAGAGACAGGATCACCGCCGGAGAAAGGCCCTGA

AGAACAAGAAGAAGCAGCTGTCCGCCGGAGGCAAGAGCCTGTCCAAAGAAG

AGGAAGAGGAGCTGAAGAGGCTGACCCGCGAGGACGAGGAGAGGAAGAAG

GAGGAGC AC GGACC A AGC AGGC TGGGAGTGA ATC C TTC C GAGGGAGGAC C T

AGGGGAGCACCAGGAGGAGGCTTCGTGCCATCTATGCAGGGCATCCCCGAGA

GCCGGTTTACCAGAACAGGAGAGGGCCTGGACGTGAGGGGCTCCCGCGGCTT

TCCTCAGGACATCCTGTTCCCATCTGATCCCCCTTTTTCCCCCCA

GCCTCAGGGCACCAACCTGTCTACAAGCAATCCACTGGGCTTCTTTCCCGACC

ACCAGCTGGATCCTGCCTTCCGCGCCAACAGCGCCAATCCCGACTGGGACTTC

AACCCAAATAAGGACACCTGGCCAGATGCCAACAAGGTCGGCGGCCAGAAC

CTGTCCACATCTAATCCTCTGGGCTTCTTTCCAGACCACCAGCTGGATCCAGC

CTTCCGGGCCAACACAGCTAACCCTGACTGGGACTTCAACCCCAATAAGGAT

ACTTGGCCCGACGCCAACAAGGTCGGCGGAAGCGGAGCTACTAACTTCAGCC

TGCTGAAGCAGGCTGGAGACGTGGAGGAGAACCCTGGACCTATGAGCCAGTC

CGAGACAAGGAGGGGCCGGAGAGGAACCAGGGAGGAGACACTGGAGAAGTG

GATCACAGCCCGCAAGAAGGCCGAGGAGCTGGAGAAGGACCTGCGGAAGAC

CAGAAAGACAATCAAGAAGCTGGAAGAAGAGAACCCATGGCTGGGCAATAT CGTGGGCATCATCAGAAAGGGCAAGGACGGCGAGGGAGCACCACCAGCAAA

GAGGCCCAGGACTGATCAGATGGAAGTCGATAGCGGACCAGGCAAGCGGCC

TCACAAGTCCGGCTTCACAGACAAGGAGAGAGAGGACCATAGGCGCCGGAA

GGCCCTGGAAAACAAGAAGAAGCAATTATCCGCCGGCGGCAAGATCCTGTCC

AAAGAGGAAGAAGAGGAGCTGAGAAGGCTGACCGACGAGGATGAGGAGAG

GAAAAGAAGGGTGGCAGGACCAAGGGTGGGCGACGTGAATCCCAGCAGGGG

AGGACCAAGAGGCGCCCCTGGCGGCGGCTTCGTGCCACAGATGGCAGGAGTG

CCAGAGAGCCCCTTTTCCAGGACAGGAGAGGGCCTGGATATC AGAGGCACCC

AGGGCTTTCCTTGGGTGTCTCCAAGCCCTCCACAGCAGCGGCTGCCACTGCTG

GAGTGCACCCCTCAGTCCCAGTCTGAGAGCAAGAAGAACAGAAGGGGCGGC

AGAGAGGACATCCTGGAGAAGTGGATCACCACACGCAGAAAAGCTGAAGAA

CTGGAAAAGGACCTGAGGAAGGCCCGCAAAACAATCAAGAAGCTGGAGGAT

GAAAATCCATGGCTGGGAAACATCATCGGCATCATCAGGAAGGGCAAGGAC

GGGGAAGGCGCACCACCTGCAAAGCGGCCTAGAACAGATCAGATGGAAATC

GATTCTGGCACCGGCAAGAGGCCACACAAGAGCGGCTTCACCGACAAGGAGC

GCGAGGATCACAGAAGGC

GCAAGGCCCTGGAGAACAAGAAGAAGCAATTAAGCAGCGGCGGCAAGAATC TGTCCAGAGAAGAAGAGGAGGAGCTGGGCCGCCTGACCGTGGAGGACGAGG

AGCGGAGAAGGCGCGTGGCAGGACCACGCACAGGCGATGTGAACCTGTCCG

GAGGAGGACCAAGGGGAGCACCTGGAGGCGGCTTCGTGCCTAGAATGGAGG

GAGTGCCTGAGTCCCCCTTCACCCGCACCGGAGAGGGCCTGGACATCAGAGG

CAATCAGGGATTCCCATGGGTGAGGCCCAGCCCACCACAGCAGCGCCTGCCA

CTGCTGGAGTGTACCCCCCAGGGCACAAACCTGTCCACCTCTAATCCCCTGGG

CTTCTTTCCTGATCATCAGCTGGACCCAGCCTTCAGGGCCAACTCCGCCAATC

CAGATTGGGACTTCAACCCGAATAAGGATACTTGGCCAGATGCAAACAAGGT

CGGAGGACAGAACCTGAGCACATCCAACCCTCTGGGCTTCTTTCCTGACCATC

AGCTGGATCCCGCCTTTCGCGCCAATACCGCCAACCCTGATTGGGACTTCAAC

CCTAATAAGGATACTTGGCCTGATGCTAATAAGGTCGGGTC^TGAGUAATTC

CGT

SEQ ID NO: 14 DELTA 1 protein

MASRSESKKmGGREEILEQWVOARKKLEELERDLRKIKKKIKKLEEE PWLGNI

KGttXiKKDREGEGAPPAKRARADQMEVDSGPRKRPFRGEFTD ERRDI-IR_RRKAL

ENKRKQLSSGGKSLSKEEEEELRKLTEEDERRERRVAGPRVGGVNPLEGGTRGAP

GGGFVPSMQGVPESPFARTGEGLDVRGNQGFPWDILFPADPPFSPQSCRPQSRSES

KKmGGREE^XEQWV^GRKKLEELERELRRARKKIKKLEDD PWLGNWGILG

KKDKDGEGAPPA RARTDQMEIDSGPRKRPLRGGFTDRERQDI-IRRRKAL N K

KQLSAGGKSLSKEEEEELKRLTREDEER EEHGPSRLGVNPSEGGPRGAPGGGF

VPSMQGIPESRFTRTGEGLDVRGSRGFPQDILFPSDPPFSPQSCRPQGTNLSTSNPL

GFFPDHQLDPAFRA SA PDWDFNPNKDTWPDA KVGGQ LSTS PLGFFPDHQ

LDP AFRANT ANPDWDFNPNKDTWPD AN VGG SG ATNF SLLKQ AGD VEENPGPM

SQSETRRGRRG REETLEKWITARKKAEELEKDLRKTRKTIKKLEEENPWLGNIV

GIIRKGKDGEGAPPAKRPRTDQMEVDSGPGKRPHKSGFTDKEREDHRRRKALEN

KKKQLSAGGKILSKEEEEELRRLTDEDEERKRRVAGPRVGDVNPSRGGPRGAPG

GGFVPQMAGVPESPFSRTGEGLDIRGTQGFPWVSPSPPQQRLPLLECTPQSQSESK

KNRRGGREDILE WITTRRKAEELEKDLRKARKTIKKLEDENPWLGNIIGIIRKGK

DGEGAPPAKRPIOOQMEIDSGTGKRI'HKSGFTDKEREDHRRI KALENK KQLSS GGKNLSREEEEELGRLTVEDEERRRRVAGPRTGDVNLSGGGPRGAPGGGFVPRIM EGVPESPFTRTGEGLDIRGNQGFPWVRPSPPQQRLPLLECTPQGTNLSTSNPLGFFP

DHQLDPAFRANSA PDWDFNPNKDTWPDA KVGGQ LSTS PLGFFPDHQLDP

AFRANTANPDWDFNPNKDTWPDAN VG Delta 1 protein SEQ ID NO: 15 Delta 2 sequence wt

GGCACCAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCT

GGATCCGGCGTTTCGCGCGAACAGCGCGAACCCGGATTGGGATTTTAACCCG

AACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCGGCCAGAACCTGAGC

ACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCG

CGCGAACACCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATACCTGG

CCGGATGCGAACAAAGTGGGCAGCCGCAGCGAAAGCAAAAAAAACCGCGGC

GGCCGCGAAGAAATTCTGGAACAGTGGGTGGGCGCGCGCAAAAAACTGGAA

GAACTGGAACGCGATCTGCGCAAAATTAAAAAAAAAATTAAAAAACTGGAA

GAAGAAAACCCGTGGCTGGGCAACATTAAAGGCATTCTGGGCAAAAAAGATC

GCGAAGGCGAAGGCGCGCCGCCGGCGAAACGCGCGCGCGCGGATCAGATGG

AAGTGGATAGCGGCCCGCGCAAACGCCCGTTTCGCGGCGAATTTACCGATAA

AGAACGCCGCGATCATCGCCGCCGCAAAGCGCTGGAAAACAAACGCAAACA

GCTGAGCAGCGGCGGCAAAAGCCTGAGCAAAGAAGAAGAAGAAGAACTGCG

CAAACTGACCGAAGAAGATGAACGCCGCGAACGCCGCGTGGCGGGCCCGCG

CGTGGGCGGCGTGAACCCGCTGGAAGGCGGCACCCGCGGCGCGCCGGGCGG

CGGCTTTGTGCCGAGCATGCAGGGCGTGCCGGAAAGCCCGTTTGCGCGCACC

GGCGAAGGCCTGGATGTGCGCGGCAACCAGGGCTTTCCGTGGGATATTCTGT

TTCCGGCGGATCCGCCGTTTAGCCCGCAGAGCTGCCGCCCGCAGAGCCGCAG

CGAAAGCAAAAAAAACCGCGGCGGCCGCGAAGAAGTGCTGGAACAGTGGGT

GAACGGCCGCAAAAAACTGGAAGAACTGGAACGCGAACTGCGCCGCGCGCG

CAAAAAAATTAAAAAACTGGAAGATGATAACCCGTGGCTGGGCAACGTGAA

AGGCATTCTGGGCAAAAAAGATAAAGATGGCGAAGGCGCGCCGCCGGCGAA

ACGCGCGCGCACCGATCAGATGGAAATTGATAGCGGCCCGCGCAAACGCCCG

CTGCGCGGCGGCTTTACCGATCGCGAACGCCAGGATCATCGCCGCCGCAAAG

CGCTGAAAAACAAAAAAAAACAGCTGAGCGCGGGCGGCAAAAGCCTGAGCA

AAGAAGAAGAAGAAGAACTGAAACGCCTGACCCGCGAAGATGAAGAACGCA

AAAAAGAAGAACATGGCCCGAGCCGCCTGGGCGTGAACCCGAGCGAAGGCG

GCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAGGGCATTCC

GGAAAGCCGCTTTACCCGCACCGGCGAAGGCCTGGATGTGCGCGGCAGCCGC

GGCTTTCCGCAGGATATTCTGTTTCCGAGCGATCCGCCGTTTAGCCCGCAGAG

CTGCCGCCCGCAGGGAAGCGGAGCTACTAACTTCAGCCTGCTGAAGCAGGCT

GGAGACGTGGAGGAGAACCCTGGACCTATGGGCACCAACCTGAGCACCAGC

AACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAA

CAGCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGAT

GCGAACAAAGTGGGCGGCCAGAACCTGAGCACCAGCAACCCGCTGGGCTTTT

TTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACACCGCGAACCCGGA

TTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGGC

AGCCAGAGCGAAACCCGCCGCGGCCGCCGCGGCACCCGCGAAGAAACCCTG

GAAAAATGGATTACCGCGCGCAAAAAAGCGGAAGAACTGGAAAAAGATCTG

CGCAAAACCCGCAAAACCATTAAAAAACTGGAAGAAGAAAACCCGTGGCTG

GGCAACATTGTGGGCATTATTCGCAAAGGCAAAGATGGCGAAGGCGCGCCGC

CGGCGAAACGCCCGCGCACCGATCAGATGGAAGTGGATAGCGGCCCGGGCA

AACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACGCGAAGATCATCGCCG CCGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAGCGCGGGCGGCAAAAT

TCTGAGCAAAGAAGAAGAAGAAGAACTGCGCCGCCTGACCGATGAAGATGA

AGAACGCAAACGCCGCGTGGCGGGCCCGCGCGTGGGCGATGTGAACCCGAG

CCGCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGCAGATGGCG

GGCGTGCCGGAAAGCCCGTTTAGCCGCACCGGCGAAGGCCTGGATATTCGCG

GCACCCAGGGCTTTCCGTGGGTGAGCCCGAGCCCGCCGCAGCAGCGCCTGCC

GCTGCTGGAATGCACCCCGCAGAGCCAGAGCGAAAGCAAAAAAAACCGCCG

CGGCGGCCGCGAAGATATTCTGGAAAAATGGATTACCACCCGCCGCAAAGCG

GAAGAACTGGAAAAAGATCTGCGCAAAGCGCGCAAAACCATTAAAAAACTG

GAAGATGAAAACCCGTGGCTGGGCAACATTATTGGCATTATTCGCAAAGGCA

AAGATGGCGAAGGCGCGCCGCCGGCGAAACGCCCGCGCACCGATCAGATGG

AAATTGATAGCGGCACCGGCAAACGCCCGCATAAAAGCGGCTTTACCGATAA

AGAACGCGAAGATCATCGCCGCCGCAAAGCGCTGGAAAACAAAAAAAAACA

GCTGAGCAGCGGCGGCAAAAACCTGAGCCGCGAAGAAGAAGAAGAACTGGG

CCGCCTGACCGTGGAAGATGAAGAACGCCGCCGCCGCGTGGCGGGCCCGCGC

ACCGGCGATGTGAACCTGAGCGGCGGCGGCCCGCGCGGCGCGCCGGGCGGC

GGCTTTGTGCCGCGCATGGAAGGCGTGCCGGAAAGCCCGTTTACCCGCACCG

GCGAAGGCCTGGATATTCGCGGCAACCAGGGCTTTCCGTGGGTGCGCCCGAG

CCCGCCGCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCGCAG

SEQ ID NO: 16 Delta 2 wt with restriction sites (Hindlll /EcoRI)

A AGCI G CCATGGCCGGCACCAACCTGAGCACCAGCAACCCGCTGGGCT

TTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACAGCGCGAACCCG

GATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGG

GCGGCCAGAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCA

GCTGGATCCGGCGTTTCGCGCGAACACCGCGAACCCGGATTGGGATTTTAAC

CCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCAGCCGCAGCGAA

AGC A A A A A A A AC CGC GGCGGC C GC GA AGAA ATTC TGGAAC AGTGGGTGGGC

GCGC GC A A A A A AC TGGA AG A AC TGG A AC GC GATC TGCGC A A A ATT A A A A A A

AAAATTAAAAAACTGGAAGAAGAAAACCCGTGGCTGGGCAACATTAAAGGC

ATTCTGGGCAAAAAAGATCGCGAAGGCGAAGGCGCGCCGCCGGCGAAACGC

GCGC GCGCGGATCAGATGGAAGTGGAT AGC GGCCCGCGCAAACGCCCGTTTC

GCGGCGAATTTACCGATAAAGAACGCCGCGATCATCGCCGCCGCAAAGCGCT

GGAAAACAAACGCAAACAGCTGAGCAGCGGCGGCAAAAGCCTGAGCAAAGA

AGAAGAAGAAGAACTGCGCAAACTGACCGAAGAAGATGAACGCCGCGAACG

CCGCGTGGCGGGCCCGCGCGTGGGCGGCGTGAACCCGCTGGAAGGCGGCACC

CGCGGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAGGGCGTGCCGGAAA

GCCCGTTTGCGCGCACCGGCGAAGGCCTGGATGTGCGCGGCAACCAGGGCTT

TCCGTGGGATATTCTGTTTCCGGCGGATC(XK CGTTTAGCCCGCAGAGC

GCCCGCAGAGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCGCGAAGAAG

TGCTGGAACAGTGGGTGAACGGCCGCAAAAAACTGGAAGAACTGGAACGCG

AACTGCGCCGCGCGCGCAAAAAAATTAAAAAACTGGAAGATGATAACCCGTG

GCTGGGCAACGTGAAAGGCATTCTGGGCAAAAAAGATAAAGATGGCGAAGG

CGC GCCGCCGGCGAAACGCGC GCGC ACCGATCAGATGGAAATTGATAGCGGC

CCGCGCAAACGCCCGCTGCGCGGCGGCTTTACCGATCGCGAACGCCAGGATC

ATCGCCGCCGCAAAGCGCTGAAAAACAAAAAAAAACAGCTGAGCGCGGGCG

GCAAAAGCCTGAGC AAAGAAGAAGAAGAAGAACTGAAACGCCTGACCCGCG

AAGATGAAGAACGCAAAAAAGAAGAACATGGCCCGAGCCGCCTGGGCGTGA ACCCGAGCGAAGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGAG CATGCAGGGCATTCCGGAAAGCCGCTTTACCCGCACCGGCGAAGGCCTGGAT

GTGCGCGGCAGCCGCGGCTTTCCGCAGGATATTCTGTTTCCGAGCGATCCGCC

GTTTAGCCCGCAGAGCTGCCGCCCGCAGGGAAGCGGAGCTACTAACTTCAGC

CTGCTGAAGCAGGCTGGAGACGTGGAGGAGAACCCTGGACCTATGGGCACC

AACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCC

GGCGTTTCGCGCGAACAGCGCGAACCCGGATTGGGATTTTAACCCGAACAAA

GATACCTGGCCGGATGCGAACAAAGTGGGCGGCCAGAACCTGAGCACCAGC

AACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAA

CACC KXJAACCCGGATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGAT

GCGAACAAAGTGGGCAGCCAGAGCGAAACCCGCCGCGGCCGCCGCGGCACC

CGCGAAGAAACCCTGGAAAAATGGATTACCGCGCGCAAAAAAGCGGAAGAA

CTGGAAAAAGATCTGCGCAAAACCCGCAAAACCATTAAAAAACTGGAAGAA

GAAAACCCGTGGCTGGGCAACATTGTGGGCATTATTCGCAAAGGCAAAGATG

GCGAAGGCGCGCCGCCGGCGAAACGCCCGCGCACCGATCAGATGGAAGTGG

ATAGCGGCCCGGGCAAACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACG

CGAAGATCATCGCCGCCGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAG

CGCGGGCGGCAAAATTCTGAGCAAAGAAGAAGAAGAAGAACTGCGCCGCCT

GACCGATGAAGATGAAGAACGCAAACGCCGCGTGGCGGGCCCGCGCGTGGG

CGATGTGAACCCGAGCCGCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTT

GTGCCGCAGATGGCGGGCGTGCCGGAAAGCCCGTTTAGCCGCACCGGCGAAG

GCCTGGATATTCGCGGCACCCAGGGCTTTCCGTGGGTGAGCCCGAGCCCGCC

GCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCGCAGAGCCAGAGCGAAAGC

AAAAAAAACCGCCGCGGCGGCCGCGAAGATATTCTGGAAAAATGGATTACCA

CCCGCCGCAAAGCGGAAGAACTGGAAAAAGATCTGCGCAAAGCGCGCAAAA

CCATTAAAAAACTGGAAGATGAAAACCCGTGGCTGGGCAACATTATTGGCAT

TATTCGCAAAGGCAAAGATGGCGAAGGCGCGCCGCCGGCGAAACGCCCGCG

CACCGATCAGATGGAAATTGATAGCGGCACCGGCAAACGCCCGCATAAAAGC

GGCTTTACCGATAAAGAACGCGAAGATCATCGCCGCCGCAAAGCGCTGGAAA

ACAAAAAAAAACAGCTGAGCAGCGGCGGCAAAAACCTGAGCCGCGAAGAAG

AAGAAGAACTGGGCCGCCTGACCGTGGAAGATGAAGAACGCCGCCGCCGCG

TGGCGGGCCCGCGCACCGGCGATGTGAACCTGAGCGGCGGCGGCCCGCGCGG

CGCGCCGGGCGGCGGCTTTGTGCCGCGCATGGAAGGCGTGCCGGAAAGCCCG

TTTACCCGCACCGGCGAAGGCCTGGATATTCGCGGCAACCAGGGCTTTCCGTG

GGTGCGCCCGAGCCCGCCGCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCG

CAGTGATGAGliAATTCCGT

SEQ ID NO: 17 delta 2 optimized

GC C G G C AC TAAC C T G T C TAG AT C AA C C C T C T G G GAT T T T T C C C C GAT C A T C AG C T G G AC C C C G CAT T T C G C G C T AAC T C T G C T AAC C C T GAC T G G GAT T T C AAC C C T AAT AAG GAC AC A TGGCCAGATGCCAACAAGGTCGGCGGCCAGAACCTGTCCACCTCTAATCCCCTGGGCT TC T T T C C T GAC C AC C AG C T G GAT CCTGCCT C AG G G C C AAC AC C G C C AAT C C C GAC T G G GAC T T C AAC C C ΑΆΑΤ AAG GAT AC C T G G C C T GAC G C TAAC AAG G T C G G C AG C C G G T C C GAG T C T A AG A AG A A T AG G G GAG G AG G GAG G AGA T C C T G GAG C AG T G G G T G G G C G C C A G AA G AG C T G GAG GAG C T GGAGCGGGACC T GAGAAAGAT CAAGAAG AAGAT CAAGAAGC TG GAG GAG GAG AAC C C C T G G C T G G G C A A C AAG G G CAT C C T G G G C AAGAAG GAT C G G GAG G GAGAG G GAG C AC C AC C T G C A A AG AG G G C C AG AG C C G A C C AG AT G GAG G T G GAT T C C G G C C C TAG G AAG C G C C CAT T C AGAG G C GAG T T T AC AGAC AAG GAG C G GAGAGAT C AC AG G C G C C G G AAG G C C C T G GAG AAC AG AG G AG C AG C T GAG C T C C G G C G G C AAG AG C C T G T C C AAG GAG GAG GAG GAG G A G C T G C G C A AG C T GAC C GAG GAG G A C GAG AG A A G G G A GAG GAG G G T G G C AG G A C C AG G G T G G GAG G C G T GAAC C C AC G GAG G GAG GAAC AG G GAG C AC C C G G A G GAG G C T T C G T G C C T T C T AT G C AG G G C G T G C C GAGAG C C CAT T T G C C AG GAC C G GAGAG G G C C T G G AC G T GAG AG G C AAT C AG G G C T T C C CAT G G GAC AT C C T G T T T C C C G C C GAT C C AC C C T T C AG C C C A C AG T C C T G C AG G C C C C AG T C T C G C AG C GAG T C C AAG AAG A AC AG AG G C G G A A G G GAG GAG G T G C T G GAG C AG T G G G T GAA G G C AG GAAGAAG C T G G AAGAAC T G GAGAG G GAG C T G A G AAG G G C C C G C AAG A GAT C A AG A AG C T G G A A GAC GAT A A T C C T T G G C T G G G C AAT G T GAAAG G CAT C C T G G G C AGAAG GAC AAG GAT G GAGAG G GAG C AC C T C C AG C AAAGAG G G C AAGAAC AGAC C AG AT G G AGAT C GAT T C C G GAC C AAG G AAG C G C C C T C T GAG G G GAG G C T TCACCGACCGGGAGAGACAGGATCACCGCCGGAGAAAGGCCCTGAAGAACAAGAAGAAG C AG C T GAG C G C C G G C G G C AAG T C T C T GAG T AAGAAGAAGAG GAG GAG C T GAAG C G G C T G ACAAGAGAGGACGAGGAGAGGAAGAAGGAGGAGCACGGACCATCCAGGCTGGGAGTGAAT CCT TCTGAGGGAGGACCAAGGGGCGCCCCTGGCGGAGGCT TCGTGCCTAGCATGCAGGGC AT C C C AGAG T C C AG G T T TAG C AG GAC AG G C GAAG G C C T G GAC G T G C G G G G C T C T AGAG G C T T T C C C C AG GAC AT C C T G T T C C C TAG C GAT C C C C C T T T T T C T C C T C AGAG C T G T AGAC C A C AG G GAAG C G GAG C T AC T AAC T T C AG C C T G C T GAAG C AG G C T G GAGAC G T G GAG GAGAAC C C T G GAC C T AT G G G C AC C AAC C T G T C C AC AT C AAC CCTCTGGGCT TCT T TC C AGAT CAT C AG C T G GAC C C AG C C T T C AG G G C C AAC AG C G C C AAT C C AGAC T G G GAC T T C AAC C C C AAT AAG GAC AC AT G G C C T GAC G C AAAC AAG G T C G GAG GAC AGAAC C T GAG C AC C T C C AAT C C A C T G G G C T T C T T T C C C GAC C A C C AG C T G GAT C C AG C C T T C C G C G C C AAC AC T G C T A A C C C T GA T T G G GAC T T C AAC C C T AAT AAG GA T AC A T G G C C T GA T G C C AAT AAG GTCGGCTC C AG AG C GAGAC AG GAG G G G C C G GAGAG GAAC C AG G GAG GAG AC AC T G GAGAAG T G GAT C AC C GCCCGCAAGAAGGCCGAGGAGCTGGAGAAGGACCTGAGGAAGACCCGCAAGACAATCAAG AAGCTGGAAGAAGAGAACCCATGGCTGGGCAATATCGTGGGCATCATCAGAAAGGGCAAG GAC G G C GAG G GAG C AC C AC C AG C AAAGAG G C C C C G C AC AGAT C AGAT G GAAG T G GAT T C C G GAC C T G G C AAG C G G C C AC A C AAG T C T G G C T T C AC C GAC A AG G A GAGA GAG GAC C A T AG G CGCCGGAAGGCCCTGGAAAACAAGAAGAAGCAAT TATCTGCCGGCGGCAAGATCCTGAGT A A AG A A GAG GAAG A G GAG C T G A GAAG G C T GAC C GAC G A G GAT GAG GAGAG GAAG C G C C G G GTGGCCGGCC C AC G C G T G G G C GAC G T GAAT C C C T C C AG G G GAG GAC C AAGAG GAG C AC C T G GAG G C G G C T T C G T G C C C C AG AT G G C C G G C G T G C C C GAG T C C C C T T T T T C T C G GAC C G G C GAGGGCCTGGATATCAGAGGCACACAGGGC T T TCCATGGGTGTCCCCCTC TCCTCCACAG C AGAG G C T G C C AC T G C T G GAG T G C AC AC C C C AGAG C C AGAG C GAAT C T AGAAGAAC AGA A

GGGGAGGCCGCGAGGACATCCTGGAAAAATGGATCACCACACGCAGAAAAGCTGAAG AAC T G GAAAAG GAC C T G C G GAAG G C C AGAAAGAC CAT C AAGAAG C T G GAG GAT GAAAAT C CAT G G C T G G G A A AC A T CAT C G G C AT C A T C C G GAAG G G C A AG G A C G G G GAAG G C G C AC C A C C T G C AAAG C G G C C T AGAAC C GAT C AGAT G GAA T C GA TAG C G G C AC AG G C AAG AG G C C AC AC A AG T C C G G C T T C AC C GA AAAGAG C G C GAG GAT C AC AGAAG G C G C AG G C C C T G GAGAAC A AG A A GAAG C AAT AAG C AG C G G C G G C A A GAAT C T G T C C AG AG A A GAG GAG GAAG AG C T G G G C C G C C T GAC AG T G GAG GAC GAG GAG C G GAGAAG G C G C G T G G C AG GAC C C AG AAC C G G C G AT G T GAAC C T G T C C G GAG GAG GAC C TAG G G GAG C AC C AG GAG G C G G C T T C G T G C C T AGAA T G G A G G G C G T G C C AG A G T C T C C C T T T AC C C G GAC AG G C G A G G G C C T G GAC AT C AG A G G C A AT C AG GGCT T TCCCTGGGT C C G C C C C T C C C C C C C T C AG C AGAGAC T G C C AC T G C T G GAAT GCACACCACAG

SEQ ID NO: 18 delta 2 codon optimized + Restriction sites

A l AG C T T G CA C CAT G GC C G G C AC T AAC C T G T C T AC A T C AAAC C C T C T G G GAT T T T TCCCC GAT CAT C AG C T G GAC C C C G CAT T T C G C G C T AAC T C T G C T AAC C C T GAC T G G GAT T T C AAC C C T AAT AG GAC AC AT G G C C AGAT G C C AAC AG G T C G G C G G C C AGAAC C T G T C C AC C T C T AA C C C C T G G G C T T C T T T C C T GAC C AC C AG C T G GAT C C T G C C T T C AG G G C C AAC AC C G C C AAT C C C G A C T G G GAC T T C A A C C C A AAT A AG G A T AC C T G G C C T G A C G C T AAC A AG G C G G C AG C C G G T C C GAG T C T AAGAAGAAT AG G G GAG GAAG G GAG GAGAT C C T G GAG C AG T G G G T G G G C G C C AG A A AG A A G C T G GAG GAG C T G GAG C G G GAC C T GAG A A AG A T C A A GAAG AAG A T C AAGAAG CT G GAG GAG GAG A A C C C C T GGC T GGGCAAT AT CAAGGGCAT CC T GGGCAAGAAG GATCGGGAGGGAGAGGGAGCACCACCTGCAAAGAGGGCCAGAGCCGACCAGATGGAGGTG GAT T C C G G C C C TAG GAAG C G C C CAT T C AGAG G C GAG T T T AC AGAC AAG GAG C G GAGAGAT C AC A G G C G C C G G A AG G C C C T G GAG A AC A AG AG G AAG C AG C T GAG C T C C G G C G G C A A GAG C C T G T C C AAG GAG G A G GAG GAG GAG C T G C G C AAG C T G AC C GAG GAG G AC G A GAG A AG G GAG AG GAG G G T G G C AG GAC C TAG G G T G G GAG G C G T GAAC C C AC T G GAG G GAG GAAC AAGAG G A G C AC C C G GAG G A G G C T T C G T G C C T T C A T G C A G G G C G T G C C T G A GAG C C CAT T T G C C AG G AC C G GAGAG G G C C T G GAC G T GAGAG G C ΑΆΤ C AG G G C T T C C CAT G G GAC AT CCTGT T TCC C G C C GAT C C AC C C T T C AG C C C AC AG T C C T G C AG G C C C C AG T C T C G C AG C GAG T C C AAGAAG AAC A GAG G C G GAAG G GAG G A G G T G C T G GAG C A G T G G G T G A AT G G C AG GAAG A AG C T GGAA GAAC T G GAGAG G GAG C T GAGAAG G G C C C G C AGAAGAT C AAG AG C T G GAAGAC GAT AAT C C T T G G C T G G G C A A T G T G A AAG G CAT C C T G G G C AAG AA G GAC AAG GAT G GAGAG G GAG C A C C T C C AG C AAAG AG G G C AAG AAC AGAC C AGAT G GAG AT C GAT T C C G GAC C AAG GAAG C G C C C T C T GAG G G GAG G C T T C AC C GAC C G G GAGAGAC AG GAT C AC C G C C G GAGAAAG G C C C T G AAGAAG AAGAAGAAGCAGCTGAGCGCCGGCGGCAAGTC TCTGAGTAAAGAAGAAGAGGAG GAG C T GAAG C G G C T GAC AAGAGAG GAC GAG GAGAG GAAGAAG GAG GAG C AC G GAC CAT C C AG G C T G G GAG T GAAT C C T T C T GAG G GAG GAC C AAG G G G C G C C C C T G G C G GAG G C T T C G T G C C TAG CAT G C AG G G CAT C C C AG G T C C AG G T T T C C AG GAC AG G C GAAG G C C T G GAC G T G C G G G G C T C T AGAG G C T T T C C C C AG GAC AT CCTGT TCC C TAG C GAT CCCCCT T T T TCT C C T CAGAGCTGTAGACCACAGGGAAGCGGAGCTAC TAA.C T TCAGCCTGCTGAAGCAGGC TGGA GAC G T G GAG G AGAAC C C T G GAC C T AT G G G C AC C AAC C T G T C C AC AT C T AAC C CTCTGGGC T T C T T T C C AGAT CAT C AG C T G GAC C C AG C C T T C AG G G C C AAC AG C G C C AT C C AG AC T G G GACT TCAACCCCAATAAGGACACATGGCCTGACGCAAACAAGGTCGGAGGACAGAACCTG AG C AC C T C C AAT C C AC TGGGCT TCT T T C C C GAC C AC C AG C T G GAT C C AG C C T T C C G C G C C AAC AC T G C T AAC C C T GAT T G G GAC T T C AAC C C T AAT AAG GAT AC AT GGCCTGATGC C AAT AAG GTCGGCTCT C AG A G C G A GAC A AG G A G G G G C C G GAGAG G AC C AG G GAG GAG AC AC T G GAGAAG T G GAT C AC C G C C C G C AAGAAG G C C GAG GAG C T G GAGAAG GAC C T GAG GAAGAC C C G C AAG C A T C AAG AAG C T G G AAGAAGAG AAC C CAT G G C G G G C AAT AT C G G G G C A T C AT C A G AA G G G C AAG G AC G G C GAG G GAG C AC C AC C A G C A A AG AG G C C C C G C A C AG A T C AG AT G GAAG T G GAT T C C G GAC C T G G C AAG C G G C C AC AC AAG T C T G G C T T C AC C GAC AAG GAG ^¬ AG AG AG GAC C AT AG G C G C C G GAAG G C C C G G AAA AC A A GAAG AG C AAT T AT C T G C C G G C G G C AAGAT C C T GAG T AAAGAAGAG GAAGAG GAG C T GAGAAG G C T GAC C GAC GAG GAT GAG GAGAG GAAG C G C C G G G T G G C C G G C C C AC G C G T G G G C GAC G T GAAT C C C T C C AG G G GAG GA C C AAGAG GAG C AC C T G GAG GCGGCT TCGTGCCC C AGAT G G C C G G C G T G C C C GAG T C C C C T T T T TCTCG GAC C G G C GAG G G C C T G GAT AT C AGAG G C AC AC AG G G C T T T C CAT GGGTGTCC C C C T C T C C T C C A C AG C AGAG G C G C C AC T G C T G GAG T G C A C AC C C C AG AG C C AGAG C G A A T C T AAGAAGAACAGAA

G G G GAG G C C G C GAG GAC AT C C T G GAAAAAT G GAT C AC C AC AC G C AGAAAAG C T GAAGAAC T G G A A AA.G GAC C T G C G GAAG G C C A G AAA GAC C AT C AAG AA G C T G GAG GAT G A A AA.T C CAT G G C T G G GAAAC AT CAT C G G CAT CAT C C G GAAG G G C AAG GAC G G G GAAG G C G C AC C AC C T G C AAAG C G G C C T AGAAC C GAT C AG AT G G AAAT C GAT AG C G G C AC AG G C AAGAG G C C AC AC A AG T C C G G C T T C A C C G A T AA GAG C G C G A G GAT C AC A GAAG G C G C AAG G C C C T G GAG AAC A AGAAGAAG C AAT T AAG C AG C G G C G G C AGAAT C T GT C C AG AG AAG AG GAG GAAG AG C T GG GCCGCC TGACAGTGGAGGACGAGGAGCGGAGAAGGCGCGTGGCAGGACCCAGAACCGGCG AT G T G AC C T G T C C G G G G A G GAC C T AG G G G A G C AC C AG G G GCGGCT TCGTGCCT G AA T G GAG G G C G T G C C AGAG T C T C C C T T TAG C C G GAC AG G C GAG G G C C T G GAC AT C AGAG G C A AT C AG G G C T T C C C T G G G T C C G C C C C T C C C C C C C T C AG C AG A GAC T G C C A C T G C T G GAAT

GC ACAC CACAG TGAT GAG AAT TCCG T SEQ ID NO: 19 delta 2 protein

MAGTTSfLSTSNPLGFFPDHQLDPAFRANSANPDWDFNP ^' NKDTWPDA KVGGQNL STSNPLGFFPDHQLDPAFRANTANPDWDFW

REEILEQWVGARKKLEELERDLRKIKKKIKKLEEENPWLGNIKGILGKKDREGEG APPAKRARADQN'IEVDSGPRKRPFRGEFTD ERRDHRRRKALENKR QLSSGGKS LSKEEEEELRKLTEEDERRERRVAGPRVGGVNPLEGGTRGAPGGGFVPSMQGVP ESPFARTGEGLDVRGNQGFPWDILFPADPPFSPQSCRPQSRSESKKNRGGREEVLE

QW\TSfGRKKLEELERELRRAR KIKKLEDD PWLGN ^? KGILGKKDKDGEGAPPA

KRARTDQMEIDSGPRKRPLRGGFTDRERQDFIRRR ALKNKKKQLSAGGKSLS E

EEEELKRLTREDEERKKEEHGPSRLGVNPSEGGPRGAPGGGFVPSMQGIPESRFTR

TGEGLDVRGSRGFPQDILFPSDPPFSPQSCRPQGSGATNFSLLKQAGDVEENPGPM

GTNLSTSNPLGFFPDHQLDPAFRANSANPDWDF P DTWPDANKVGGQNLSTS

NPLGFFPDFiQL PAFRANTANPDWDFNPNKDTWPDAN VGSQSETRRGRRGTR

EETLEKWITARK AEELEKDLR TRKTEK LEEENPWTLGNIVGIIRKGKDGEGAPP

A RI ^> RTDQME\T)SGPGKRPH SGFTDKEi EDHRJiR ALE K QLSAGGKILSK

EEEEELRRLTDEDEERKRRVAGPRVGD TN ^T PSRGGPRGAPGGGFWQMAG\ ^/ TESP

FSRTGEGLDIRGTQGFPWVSPSPPQQRLPLLECTPQSQSESKKNRRGGREDRvEKW

ITTRRKAEELE DLRKARKT1KKLEDENPWLGNIIGIIRKGKDGEGAPPA RPRTD

QMEID S GTGKRPHK S GF TDKEREDHRRR ALEN K QL S S GGK LS REEEEELG

RLTVEDEERRRRVAGPRTGDVNLSGGGPRGAPGGGFVPRMEGVPESPFTRTGEG

LDIRGNQGFPWVRPSPPQQRLPLLECTPQ

SEQ ID NO: 20: delta 3 wt

GGCACCAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCT

GGATCCGGCGTTTCGCGCGAACAGCGCGAACCCGGATTGGGATTTTAACCCG

AACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCGGCCAGAACCTGAGC

ACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCG

CGCGAACACCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATACCTGG

CCGGATGCGAACAAAGTGGGCAGCCGCAGCGAAAGCAAAAAAAACCGCGGC

GGCCGCGAAGAAATTCTGGAACAGTGGGTGGGCGCGCGCAAAAAACTGGAA

GAACTGGAACGCGATCTGCGCAAAATTAAAAAAAAAATTAAAAAACTGGAA

GAAGAAAACCCGTGGCTGGGCAACATTAAAGGCATTCTGGGCAAAAAAGATC

GCGAAGGCGAAGGCGCGCCGCCGGCGAAACGCGCGCGCGCGGATCAGATGG

AAGTGGATAGCGGCCCG(XK AAACGCCCGTTTCGCGGCGAATTTACCGATAA

AGAACGCCGCGATCATCGCCGCCGCAAAGCGCTGGAAAACAAACGCAAACA

GCTGAGCAGCGGCGGCAAAAGCCTGAGCAAAGAAGAAGAAGAAGAACTGCG

CAAACTGACCGAAGAAGATGAACGCCGCGAACGCCGCGTGGCGGGCCCGCG

CGTGGGCGGCGTGAACCCGCTGGAAGGCGGCACCCGCGGCGCGCCGGGCGG

CGGCTTTGTGCCGAGCATGCAGGGCGTGCCGGAAAGCCCGTTTGCGCGCACC

GGCGAAGGCCTGGATGTGCGCGGCAACCAGGGCTTTCCGTGGGATATTCTGT

TTCCGGCGGATCCGCCGTTTAGCCCGCAGAGCTGCCGCCCGCAGAGCCGCAG

CGAAAGCAAAAAAAACCGCGGCGGCCGCGAAGAAGTGCTGGAACAGTGGGT

GAACGGCCGCAAAAAACTGGAAGAACTGGAACGCGAACTGCGCCGCGCGCG

CAAAAAAATTAAAAAACTGGAAGATGATAACCCGTGGCTGGGCAACGTGAA

AGGCATTCTGGGCAAAAAAGATAAAGATGGCGAAGGCGCGCCGCCGGCGAA

ACGCGCGCGCACCGATCAGATGGAAATTGATAGCGGCCCGCGCAAACGCCCG

CTGCGCGGCGGCTTTACCGATCGCGAACGCCAGGATCATCGCCGCCGCAAAG

CGCTGAAAAACAAAAAAAAACAGCTGAGCGCGGGCGGCAAAAGCCTGAGCA

AAGAAGAAGAAGAAGAACTGAAACGCCTGACCCGCGAAGATGAAGAACGCA

AAAAAGAAGAACATGGCCCGAGCCGCCTGGGCGTGAACCCGAGCGAAGGCG

GCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAGGGCATTCC

GGAAAGCCGCTTTACCCGCACCGGCGAAGGCCTGGATGTGCGCGGCAGCCGC

GGCTTTCCGCAGGATATTCTGTTTCCGAGCGATCCGCCGTTTAGCCCGCAGAG

CTGCCGCCCGCAGGGCACCAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTC CGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACAGCGCGAACCCGGATTG

GGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCGGC

CAGAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGA

TCCGGCGTTTCGCGCGAACACCGCGAACCCGGATTGGGATTTTAACCCGAAC

AAAGATACCTGGCCGGATGCGAACAAAGTGGGCGGAAGCGGAGCTAC TAAC T TC

AGCC T GC T GAAGCAGGC T GGAGACGT GGAGGAGAACCC T GGACC TATGGGCACCAACC

TGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCG

TTTCGCGCGAACAGCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATA

CCTGGCCGGATGCGAACAAAGTGGGCGGCCAGAACCTGAGCACCAGCAACCC

GCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACACCG

CGAACCCGGATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAA

CAAAGTGGGCAGCCAGAGCGAAACCCGCCGCGGCCGCCGCGGCACCCGCGA

AGAAACCCTGGAAAAATGGATTACCGCGCGCAAAAAAGCGGAAGAACTGGA

AAAAGATCTGCGCAAAACCCGCAAAACCATTAAAAAACTGGAAGAAGAAAA

CCCGTGGCTGGGCAACATTGTGGGCATTATTCGCAAAGGCAAAGATGGCGAA

GGCGCGCCGCCGGCGAAACGCCCGCGCACCGATCAGATGGAAGTGGATAGC

GGCCCGGGCAAACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACGCGAA

GATCATCGCCGCCGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAGCGCG

GGCGGCAAAATTCTGAGCAAAGAAGAAGAAGAAGAACTGCGCCGCCTGACC

GATGAAGATGAAGAACGCAAACGCCGCGTGGCGGGCCCGCGCGTGGGCGAT

GTGAACCCGAGCCGCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGC

CGCAGATGGCGGGCGTGCCGGAAAGCCCGTTTAGCCGCACCGGCGAAGGCCT

GGATATTCGCGGCACCCAGGGCTTTCCGTGGGTGAGCCCGAGCCCGCCGCAG

CAGCGCCTGCCGCTGCTGGAATGCACCCCGCAGAGCCAGAGCGAAAGCAAAA

AAAACCGCCGCGGCGGCCGCGAAGATATTCTGGAAAAATGGATTACCACCCG

CCGCAAAGCGGAAGAACTGGAAAAAGATCTGCGCAAAGCGCGCAAAACCAT

TAAAAAACTGGAAGATGAAAACCCGTGGCTGGGCAACATTATTGGCATTATT

CGCAAAGGCAAAGATGGCGAAGGCGCGCCGCCGGCGAAACGCCCGCGCACC

GATC AGATGGAAATTGATAGCGGCACCGGCAAACGCCCGCATAAAAGCGGCT

TTACCGATAAAGAACGCGAAGATCATCGCCGCCGCAAAGCGCTGGAAAACAA

AAAAAAACAGCTGAGCAGCGGCGGCAAAAACCTGAGCCGCGAAGAAGAAGA

AGAACTGGGCCGCCTGACCGTGGAAGATGAAGAACGCCGCCGCCGCGTGGCG

GGCCCGCGCACCGGCGATGTGAACCTGAGCGGCGGCGGCCCGCGCGGCGCGC

CGGGCGGCGGCTTTGTGCCGCGCATGGAAGGCGTGCCGGAAAGCCCGTTTAC

CCGCACCGGCGAAGGCCTGGATATTCGCGGCAACCAGGGCTTTCCGTGGGTG

CGCCCGAGCCCGCCGCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCGCAGG

GCACCAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATC ATCAGCTG

GATCCGGCGTTTCGCGCGAACAGCGCGAACCCGGATTGGGATTTTAACCCGA

ACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCGGCCAGAACCTGAGCA

CCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGC

GCGAACACCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATACCTGGC

CGGATGCGAACAAAGTGGGC

SEQ ID NO: 21 delta 3 wt + with restriction sites (HindDI EcoRI)

A AGCT T GCACCATGGCCGGCACCAACCTGAGCACCAGCAACCCGCTGGGCTTTT TTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACAGCGCGAACCCGGA

TTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGT

GGCCAGAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCT

GGATCCGGCGTTTCGCGCGAACACCGCGAACCCGGATTGGGATTTTAACCCG AACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCAGCCGCAGCGAAAGC AAAAAAAACCGCGGCGGCCGCGAAGAAATTCTGGAACAGTGGGTGGGCGCG

CGCAAAAAACTGGAAGAACTGGAACGCGATCTGCGCAAAATTAAAAAAAAA

ATTAAAAAACTGGAAGAAGAAAACCCGTGGCTGGGCAACATTAAAGGCATTC

TGGGCAAAAAAGATCGCGAAGGCGAAGGCGCGCCGCCGGCGAAACGCGCGC

GCGCGGATCAGATGGAAGTGGATAGCGGCCCGCGCAAACGCCCGTTTCGCGG

CGAATTTACCGATAAAGAACGCCGCGATCATCGCCGCCGCAAAGCGCTGGAA

AACAAACGCAAACAGCTGAGCAGCGGCGGCAAAAGCCTGAGCAAAGAAGAA

GAAGAAGAACTGCGCAAACTGACCGAAGAAGATGAACGCCGCGAACGCCGC

GTGGCGGGCCCGCGCGTGGGCGGCGTGAACCCGCTGGAAGGCGGCACCCGCG

GCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAGGGCGTGCCGGAAAGCCC

GTTTGCGCGCACCGGCGAAGGCCTGGATGTGCGCGGCAACCAGGGCTTTCCG

TGGGATATTCTGTTTCCGGCGGATCCGCCGTTTAGCCCGCAGAGCTGCCGCCC

GCAGAGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCGCGAAGAAGTGCT

GGAACAGTGGGTGAACGGCCGCAAAAAACTGGAAGAACTGGAACGCGAACT

GCGCCGCGCGCGCAAAAAAATTAAAAAACTGGAAGATGATAACCCGTGGCTG

GGCAACGTGAAAGGCATTCTGGGCAAAAAAGATAAAGATGGCGAAGGCGCG

CCGCCGGCGAAACGCGCGCGCACCGATCAGATGGAAATTGATAGCGGCCCGC

GCAAACGCCCGCTGCGCGGCGGCTTTACCGATCGCGAACGCCAGGATCATCG

CCGCCGCAAAGCGCTGAAAAACAAAAAAAAACAGCTGAGCGCGGGCGGCAA

AAGCCTGAGCAAAGAAGAAGAAGAAGAACTGAAACGCCTGACCCGCGAAGA

TGAAGAACGCAAAAAAGAAGAACATGGCCCGAGCCGCCTGGGCGTGAACCC

GAGCGAAGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATG

CAGGGCATTCCGGAAAGCCGCTTTACCCGCACCGGCGAAGGCCTGGATGTGC

GCGGCAGCCGCGGCTTTCCGCAGGATATTCTGTTTCCGAGCGATCCGCCGTTT

AGCCCGCAGAGCTGCCGCCCGCAGGGCACCAACCTGAGCACCAGCAACCCGC

TGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACAGCGCG

AACCCGGATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACA

AAGTGGGCGGCCAGAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGA

TCATCAGCTGGATCCGGCGTTTCGCGCGAACACCGCGAACCCGGATTGGGAT

TTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCGGAAGCGG

AG C TAG AAC T GAG C C T G C GAAG C AG G C T G GAG AC G T G GAG GAGAAC C C T G GAG C T A

TGGGCACCAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCA

GCTGGATCCGGCGTTTCGCGCGAACAGCGCGAACCCGGATTGGGATTTTAAC

CCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCGGCCAGAACCTG

AGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTT

TCGCGCGAACACCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATACC

TGGCCGGATGCGAACAAAGTGGGCAGCCAGAGCGAAACCCGCCGCGGCCGC

CGCGGCACCCGCGAAGAAACCCTGGAAAAATGGATTACCGCGCGCAAAAAA

GCGG A AGA AC TGGA A A A AGATC TGC GC A A A ACC C GC A A AAC C ATT A A A A A A

CTGGAAGAAGAAAACCCGTGGCTGGGCAACATTGTGGGCATTATTCGCAAAG

GCAAAGATGGCGAAGGCGCGCCGCCGGCGAAACGCCCGCGCACCGATCAGA

TGGAAGTGGATAGCGGCCCGGGCAAACGCCCGCATAAAAGCGGCTTTACCGA

TAAAGAACGCGAAGATCATCGCCGCCGCAAAGCGCTGGAAAACAAAAAAAA

ACAGCTGAGCGCGGGCGGCAAAATTCTGAGCAAAGAAGAAGAAGAAGAACT

GCGCCGCCTGACCGATGAAGATGAAGAACGCAAACGCCGCGTGGCGGGCCC

GCGCGTGGGCGATGTGAACCCGAGCCGCGGCGGCCCGCGCGGCGCGCCGGGC

GGCGGCTTTGTGCCGCAGATGGCGGGCGTGCCGGAAAGCCCGTTTAGCCGCA

CCGGCGAAGGCCTGGATATTCGCGGCACCCAGGGCTTTCCGTGGGTGAGCCC GΛG{ ·C ^' ( _ί { ·( }{ ·Λ( fC _ί { ·C Ί·( iC ·{ iCΊ ( _ί { Ί·{ iGΛ ΛT( H:^Λ{ ·( ^Λ( LΛ{ iC ^\G

AGCGAAAGCAAAAAAAACCGCCGCGGCGGCCGCGAAGATATTCTGGAAAAA

TGGATTACCACCCGCCGCAAAGCGGAAGAACTGGAAAAAGATCTGCGCAAA

GCGCGCAAAACCATTAAAAAACTGGAAGATGAAAACCCGTGGCTGGGCAAC

ATTATTGGCATTATTCGC AAAGGCAAAGATGGCGAAGGCGCGCCGCCGGCGA

AACGCCCGCGCACCGATCAGATGGAAATTGATAGCGGCACCGGCAAACGCCC

GCATAAAAGCGGCTTTACCGATAAAGAACGCGAAGATCATCGCCGCCGCAAA

GCGCTGGAAAACAAAAAAAAACAGCTGAGCAGCGGCGGCAAAAACCTGAGC

CGCGAAGAAGAAGAAGAACTGGGCCGCCTGACCGTGGAAGATGAAGAACGC

CGCCGCCGCGTGGCGGGCCCGCGCACCGGCGATGTGAACCTGAGCGGCGGCG

GCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGCGCATGGAAGGCGTGCC

GGAAAGCCCGTTTACCCGCACCGGCGAAGGCCTGGATATTCGCGGCAACCAG

GGCTTTCCGTGGGTGCGCCCGAGCCCGCCGCAGCAGCGCCTGCCGCTGCTGG

AATGCACCCCGCAGGGCACCAACCTGAGCACCAGCAACCCGCTGGGCTTTTT

TCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACAGCGCGAACCCGGAT

TGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCG

GCCAGAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTG

GATCCGGCGTTTCGCGCGAACACCGCGAACCCGGATTGGGATTTTAACCCGA

ACAAAGATACCTGGCCGGATGCGAACAAAGTGGGC TGAT GAGUAAT T CCGT

SEQ ID NO: 22: delta 3 optimized

GCCGGCACCAATCTGTCTACCTCAAATCCCCTGGGCTTCTTCCCCGATCATCA GCTGGACCCTGCCTTCCGAGCAAATTCCGCTAATCCTGATTGGGATTTCAACC CAAATAAGGACACATGGCCAGATGCCAACAAGGTCGGCGGCCAGAACCTGTC

CACCTCTAATCCTCTGGGCTTCTTTCCAGACCACCAGCTGGATCCCGCCTTCA

GGGCCAACACAGCCAATCCCGACTGGGACTTCAACCCTAATAAGGACACCTG

GCCTGACGCCAACAAGGTCGGCAGCAGGTCCGAGTCTAAGAAGAATAGGGG

AGGAAGGGAGGAGATCCTGGAGCAGTGGGTGGGAGCACGCAAGAAGCTGGA

GGAGCTGGAGCGGGACCTGAGAAAGATCAAGAAGAAGATCAAGAAGCTGGA

GGAGGAGAACCCCTGGCTGGGCAATATCAAGGGCATCCTGGGCAAGAAGGA

TCGGGAGGGAGAGGGAGCACCACCTGCAAAGAGGGCCAGAGCCGACCAGAT

GGAGGTGGATTCCGGACCAAGGAAGCGCCCTTTCAGAGGAGAGTTTACAGAC

AAGGAGCGGAGAGATCACAGGCGCCGGAAGGCCCTGGAGAACAAGCGGAAG

CAGCTGAGCTCCGGCGGCAAGAGCCTGTCCAAGGAGGAGGAGGAGGAGCTG

AGAAAGCTGACCGAGGAGGACGAGAGAAGGGAGAGGAGGGTGGCCGGCCCC

AGGGTGGGCGGCGTGAACCCTCTGGAGGGAGGAACAAGGGGAGCACCAGGA

GGAGGCTTCGTGCCTTCCATGCAGGGCGTGCCCGAGTCTCCTTTTGCCAGGAC

CGGAGAGGGCCTGGACGTGCGCGGCAATCAGGGCTTCCCATGGGACATCCTG

TTTCCCGCCGATCCACCCTTCTCTCCCCAGAGCTGCAGGCCTCAGTCTCGCAG

CGAGTCCAAGAAGAACAGAGGCGGAAGGGAGGAGGTGCTGGAGCAGTGGGT

GAATGGCAGGAAGAAGCTGGAAGAACTGGAGAGGGAGCTGAGAAGGGCCCG

CAAGAAGATCAAGAAGCTGGAAGACGATAATCCTTGGCTGGGCAATGTGAAA

GGCATCCTGGGCAAGAAGGACAAGGATGGAGAGGGAGCACCTCCAGCAAAG

AGGGCAAGAACAGACCAGATGGAGATCGATTCTGGACCAAGGAAGCGCCCC

CTGAGGGGAGGCTTCACCGACCGGGAGAGACAGGATCACCGCCGGAGAAAG

GCCCTGAAGAACAAGAAGAAGCAGCTGAGCGCCGGCGGCAAGTCTCTGAGT

AAAGAAGAAGAGGAGGAGCTGAAGCGGCTGACCAGAGAGGACGAGGAGCG

GAAGAAGGAGGAGCACGGCCCAAGCAGACTGGGAGTGAATCCATCCGAGGG

AGGACCTAGAGGCGCCCCTGGCGGCGGCTTCGTGCCTTCTATGCAGGGCATC CCAGAGAGCAGGTTTACCAGGACAGGCGAAGGCCTGGACGTGCGGGGCTCC A

GAGGCTTTCCCCAGGACATCCTGTTCCCTTCTGATCCCCCTTTTTCCCCACAGT

CTTGTAGGCCCCAGGGCACCAACCTGTCCACATCTAACCCACTGGGCTTCTTT

CCTGATCACCAGCTGGATCCAGCCTTCCGCGCCAACTCCGCCAATCCAGACTG

GGACTTC AACCCCAATAAGGACACATGGCCTGATGCTAACAAGGTCGGAGGC

CAGAACCTGAGCACCTCCAATCCCCTGGGCTTCTTTCCTGACCACCAGCTGGA

TCCTGCCTTCCGCGCCAACACAGCTAACCCTGATTGGGACTTCAACCCAAATA

AGGATACCTGGCCTGATGCAAACAAGGTCGGAGGAAGCGGAGCTACTAACTT

CAGCCTGCTGAAGCAGGCTGGAGACGTGGAGGAGAACCCTGGACCTATGGGC

ACCAACCTGTCTACAAGCAATCCACTGGGCTTCTTTCCCGACCATCAGCTGGA

CCCAGCCTTCAGGGCCAACAGCGCCAACCCTGACTGGGACTTCAACCCAAAT

AAGGACACGTGGCCTGATGCCAACAAGGTCGGAGGACAAAACCTGTCCACCT

CTAACCCCCTGGGCTTCTTTCCCGATCATCAATTAGACCC AGCCTTCCGCGCT

AACACTGCTAACCCTGACTGGGACTTCAACCCGAATAAGGATACTTGGCCTG

ATGC C A AT A AGGTC GGC AGC C AGTC C GAGAC A AGGAGGGGC C GGAGAGGA A

CCAGGGAGGAGACACTGG AG AAGTGGATCACCGCCAGAAAGAAGGCCGAGG

AGCTGGAGAAGGACCTGAGGAAGACCCGCAAGACAATCAAGAAGCTGGAAG

AAGAGAACCCTTGGCTGGGCAATATCGTGGGCATCATCAGAAAGGGCAAGGA

CGGCGAGGGAGCACCACCAGCCAAGAGGCCACGCACAGATCAGATGGAAGT

GGATAGC GG AGCAGGC AAG AG GCCTC AC AAGTCCGGCTTCACCGACAAGGA

GAGGGAGGACCATAGGCGCCGGAAGGCCCTGGAAAACAAGAAGAAGCAATT

ATCCGCCGGCGGCAAGATCCTGTCTAAAGAAGAGGAAGAAGAGC

TGAGAAGGCTGACCGACGAGGATGAGGAGAGGAAGAGGAGGGTGGCAGGAC

CTAGAGTGGGCGACGTGAATCCATCCAGGGGAGGACCAAGAGGAGCACCAG

GAGGCGGCTTCGTGCCACAGATGGCAGGAGTGCCAGAGAGCCCCTTTTCCAG

GACAGGAGAGGGCCTGGATATCAGGGGAACCCAGGGCTTTCCTTGGGTGTCT

CCAAGCCCTCCACAGCAGCGGCTGCCACTGCTGGAGTGCACACCCCAGTCCC

AGTCTGAGAGCAAGAAGAACAGAAGGGGCGGCAGAGAGGACATCCTGGAAA

AATGGATCACCACACGCAGAAAAGCTGAAGAACTGGAAAAGGACCTGCGGA

AGGCCAGAAAGACCATCAAGAAGCTGGAGGATGAAAATCCATGGCTGGGAA

ATATCATCGGCATCATCCGGAAGGGCAAGGACGGGGAAGGCGCACCACCTGC

AAAGCGGCCCAGGACCGATCAGATGGAAATCGATTCTGGAACCGGCAAGCG

GCCTCACAAGAGTGGCTTCACCGATAAGGAGAGAGAGGATCACAGAAGGCG

CAAGGCCCTGGAGAACAAGAAGAAGCAATTAAGCAGCGGCGGCAAGAATCT

GTCCAGAGAAGAGGAAGAGGAGCTGGGCAGACTGACAGTGGAGGACGAGGA

GCGGAGAAGGCGCGTGGCAGGACCAAGAACCGGCGATGTGAACCTGTCCGG

AGGAGGACCAAGGGGAGCACCTGGGGGAGGCTTCGTGCCAAGGATGGAGGG

AGTGCCTGAGTCCCCCTTCACCAGAACCGGCGAAGGCCTGGACATCAGGGGC

AATCAGGGATTCCCATGGGTGCGGCCCTCCCCACCCCAGCAGAGACTGCCTC

TGCTGGAGTGTACCCCACAGGGCACTAACCTGTCCACCTCTAACCCGTTAGGC

TTCTTTCCTGACCATCAATTAGATCCCGCCTTCCGGGCCAACAGCGCCAATCC

TGATTGGGACTTCAACCCGAATAAGGACACCTGGCCCGACGCAAACAAGGTC

GGAGGGCAAAACCTGAGCACCTCCAACCCTTTAGGCTTCTTTCCAGATCATCA

GCTGGATCCAGCCTTTAGAGCCAATACCGCCAACCCTGACTGGGATTTCAACC

CTAACAAAGATACCTGGCCCGACGCTAACAAAGTGGGA

SEQ ID NO: 23 delta 3 codon optimized with restriction sites (Hindin/EcoRl)

A AGCTTGC^CCATGOCCGGCACCAATCTGTCTACCTCAAATCCCCTGGGCTT CTTCCCCGATCATCAGCTGGACCCTGCCTTCCGAGCAAATTCCGCTAATCCTG ATTGGGATTTCAACCCAAATAAGGACACATGGCCAGATGCCAACAAGGTCGG

CGGCCAGAACCTGTCCACCTCTAATCCTCTGGGCTTCTTTCCAGACCACCAGC

TGGATCCCGCCTTCAGGGCCAACACAGCCAATCCCGACTGGGACTTCAACCC

TAATAAGGACACCTGGCCTGACGCCAACAAGGTCGGCAGCAGGTCCGAGTCT

AAGAAGAATAGGGGAGGAAGGGAGGAGATCCTGGAGCAGTGGGTGGGAGCA

CGCAAGAAGCTGGAGGAGCTGGAGCGGGACCTGAGAAAGATCAAGAAGAAG

ATCAAGAAGCTGGAGGAGGAGAACCCCTGGCTGGGCAATATCAAGGGCATCC

TGGGCAAGAAGGATCGGGAGGGAGAGGGAGCACCACCTGCAAAGAGGGCCA

GAGCCGACCAGATGGAGGTGGATTCCGGACCAAGGAAGCGCCCTTTCAGAGG

AGAGTTTACAGACAAGGAGCGGAGAGATCACAGGCGCCGGAAGGCCCTGGA

GAAC AAGC GGA AGC AGC TGAGC TC C GGC GGC AAGAGC CTGTC C A AGGAGG A

GGAGGAGGAGCTGAGAAAGCTGACCGAGGAGGACGAGAGAAGGGAGAGGA

GGGTGGCCGGCCCCAGGGTGGGCGGCGTGAACCCTCTGGAGGGAGGAACAA

GGGGAGCACCAGGAGGAGGCTTCGTGCCTTCCATGCAGGGCGTGCCCGAGTC

TCCTTTTGCCAGGACCGGAGAGGGCCTGGACGTGCGCGGCAATCAGGGCTTC

CCATGGGACATCCTGTTTCCCGCCGATCCACCCTTCTCTCCCCAGAGCTGCAG

GCCTCAGTCTCGCAGCGAGTCCAAGAAGAACAGAGGCGGAAGGGAGGAGGT

GCTGGAGCAGTGGGTGAATGGCAGGAAGAAGCTGGAAGAACTGGAGAGGGA

GCTGAGAAGGGCCCGCAAGAAGATCAAGAAGCTGGAAGACGATAATCCTTG

GCTGGGCAATGTGAAAGGCATCCTGGGCAAGAAGGACAAGGATGGAGAGGG

AGCACCTCCAGCAAAGAGGGCAAGAACAGACCAGATGGAGATCGATTCTGG

ACCAAGGAAGCGCCCCCTGAGGGGAGGCTTCACCGACCGGGAGAGACAGGA

TCACCGCCGGAGAAAGGCCCTGAAGAACAAGAAGAAGCAGCTGAGCGCCGG

CGGCAAGTCTCTGAGTAAAGAAGAAGAGGAGGAGCTGAAGCGGCTGACCAG

AGAGGACGAGGAGCGGAAGAAGGAGGAGCACGGCCCAAGCAGACTGGGAGT

GAATCCATCCGAGGGAGGACCTAGAGGCGCCCCTGGCGGCGGCTTCGTGCCT

TCTATGCAGGGCATCCCAGAGAGCAGGTTTACCAGGACAGGCGAAGGCCTGG

ACGTGCGGGGCTCCAGAGGCTTTCCCCAGGACATCCTGTTCCCTTCTGATCCC

CCTTTTTCCCCACAGTCTTGTAGGCCCCAGGGCACCAACCTGTCCACATCTAA

CCCACTGGGCTTCTTTCCTGATCACCAGCTGGATCCAGCCTTCCGCGCCAACT

CCGCCAATCCAGACTGGGACTTCAACCCCAATAAGGACACATGGCCTGATGC

TAACAAGGTCGGAGGCCAGAACCTGAGCACCTCCAATCCCCTGGGCTTCTTTC

CTGACCACCAGCTGGATCCTGCCTTCCGCGCCAACACAGCTAACCCTGATTGG

GACTTCAACCCAAATAAGGATACCTGGCCTGATGCAAACAAGGTCGGAGGAA

GCGGAGCTACTAACTTCAGCCTGCTGAAGCAGGCTGGAGACGTGGAGGAGAA

CCCTGGACCTATGGGCACCAACCTGTCTACAAGCAATCCACTGGGCTTCTTTC

CCGACCATCAGCTGGACCCAGCCTTCAGGGCCAACAGCGCCAACCCTGACTG

GGACTTCAACCCAAATAAGGACACGTGGCCTGATGCCAACAAGGTCGGAGGA

CAAAACCTGTCCACCTCTAACCCCCTGGGCTTCTTTCCCGATCATCAATTAGA

CCCAGCCTTCCGCGCTAACACTGCTAACCCTGACTGGGACTTCAACCCGAATA

AGGATACTTGGCCTGATGCCAATAAGGTCGGCAGCCAGTCCGAGACAAGGAG

GGGCCGGAGAGGAACCAGGGAGGAGACACTGGAGAAGTGGATCACCGCCAG

AAAGAAGGCCGAGGAGCTGGAGAAGGACCTGAGGAAGACCCGCAAGACAAT

CAAGAAGCTGGAAGAAGAGAACCCTTGGCTGGGCAATATCGTGGGCATCATC

AGAAAGGGCAAGGACGGCGAGGGAGCACCACCAGCCAAGAGGCCACGCACA

GATCAGATGGAAGTGGATAGCGGACCAGGCAAGAGGCCTCACAAGTCCGGCT

TCACCGACAAGGAGAGGGAGGACCATAGGCGCCGGAAGGCCCTGGAAAACA

AGAAGAAGCAATTATCCGCCGGCGGCAAGATCCTGTCTAAAGAAGAGGAAG

AAGAGC TGAGAAGGCTGACCGACGAGGATGAGGAGAGGAAGAGGAGGGTGGCAGGAC

CTAGAGTGGGCGACGTGAATCCATCCAGGGGAGGACCAAGAGGAGCACCAG

GAGGCGGCTTCGTGCCACAGATGGCAGGAGTGCCAGAGAGCCCCTTTTCCAG

GACAGGAGAGGGCCTGGATATCAGGGGAACCCAGGGCTTTCCTTGGGTGTCT

CCAAGCCCTCCACAGC AGCGGCTGCCACTGCTGGAGTGCACACCCCAGTCCC

AGTCTGAGAGCAAGAAGAACAGAAGGGGCGGCAGAGAGGACATCCTGGAAA

AATGGATCACCACACGCAGAAAAGCTGAAGAACTGGAAAAGGACCTGCGGA

AGGCCAGAAAGACCATCAAGAAGCTGGAGGATGAAAATCCATGGCTGGGAA

ATATCATCGGCATC ATCCGGAAGGGCAAGGACGGGGAAGGCGCACCACCTGC

AAAGCGGCCCAGGACCGATCAGATGGAAATCGATTCTGGAACCGGCAAGCG

GCCTCACAAGAGTGGCTTCACCGATAAGGAGAGAGAGGATCACAGAAGGCG

CAAGGCCCTGGAGAACAAGAAGAAGCAATTAAGCAGCGGCGGCAAGAATCT

GTCCAGAGAAGAGGAAGAGGAGCTGGGCAGACTGACAGTGGAGGACGAGGA

GCGGAGAAGGCGCGTGGCAGGACCAAGAACCGGCGATGTGAACCTGTCCGG

AGGAGGACCAAGGGGAGCACCTGGGGGAGGCTTCGTGCCAAGGATGGAGGG

AGTGCCTGAGTCCCCCTTCACCAGAACCGGCGAAGGCCTGGACATCAGGGGC

AATCAGGGATTCCCATGGGTGCGGCCCTCCCCACCCCAGCAGAGACTGCCTC

TGCTGGAGTGTACCCCACAGGGCACTAACCTGTCCACCTCTAACCCGTTAGGC

TTCTTTCCTGACCATCAATTAGATCCCGCCTTCCGGGCCAACAGCGCCAATCC

TGATTGGGACTTCAACCCGAATAAGGACACCTGGCCCGACGCAAACAAGGTC

GGAGGGCAAAACCTGAGCACCTCCAACCCTTTAGGCTTCTTTCCAGATCATCA

GCTGGATCCAGCCTTTAGAGCCAATACCGCCAACCCTGACTGGGATTTCAACC

CTAACAAAGATACCTGGCCCGACGCTAACAAAGTGGGATGATGAG AATTCC

GT

SEQ ID NO: 24 Delta 3 protein

MAGTM.,STSNPLGFFPDIIQLDPAFRANSANPDWDFNPN DTWPDANKVGGQN1..

STSNPLGFFPDHQLDPAFRANTANPDWDFNPNKDTWPDANKVGSRSESKKNRGG

REEILEQWVGAR KLEELERDLRKI KKIKKLEEENPWLGNI GILG KDREGEG

APPAKRARADQMEVDSGPRKRPFRGEFTDKERRDFiRRRKALENKRKQLSSGGKS

LSKEEEEELRKLTEEDERRERRVAGPRVGGVTSiPLEGGTRGAPGGGFVPSMQG-VP

ES PF ARTGEGLD VRGNQGFP WDILFP ADPPF S PQ SCRPQ SRSESKKNRG GREE VLE

QWVNGRKKLEELERELRRAJ^KI KLEDDNPWLGNVKGILGK D DGEGAPPA

KRARTD QMED3 S GPRKRPLRGGF TDRERQDFIRRRK ALKNKKKQL S AGGK SL SKE

EEEELKRL REDEERKKEEHGPSRLGVNPSEGGPRGAPGGGFVPSMQGIPESRFTR

TGEGLDVRGSRGFPQDILFPSDPPFSPQSCRPQGTNLSTSNPLGFFPDHQLDPAFRA

NSANPDWDFNPN DTVVPDANKVGGQNLSTSNPLGFFPDHQLDPAFRANTA PD

WDFNPNKDTWPDANKVGGSGATNFSLLKQAGD\¾ENPGPMGTNLSTSNPLGFFP

DHQLDPAFRANSANPDWDF PNKDTWPDA.NKVGGQNLSTSNPLGFFPDHQLDP

AFRANTANPDWDFNPNKDTWPDANKVGSQSETRRGRRGTREETLEKWITAR K

AEELEKDLRKTRKTIKKLEEENPWLGNIVGIIRXGKDGEGAPPAKRPRTDQMEVD

SGPGKRPHKSGFTDKEREDHRRRKALENKKKQLSAGGKILSKEEEEELRRLTDED

EERKRRVAGPRVGDVNPSRGGPRG-APGGGFVPQMAG-VPESPFSRTGEGLDIRGT

QGFPWVSPSPPQQRLPLLECTPQSQSESKKNRRGGREDILEKWITTRRKAEELEKD

LRKARKTIKKLEDENPWLGNnGlIRKGKDGEGAPPAKRPRTDQMEIDSGTGKRPH

KSGFTDKEREDHRRRKALENKKKQLSSGGKNLSREEEEELGRLTVEDEERRRRV

AGPRTGDVNLSGGGPRGAPGGGFVPRMEGVPESPFTRTGEGLDIRGNQGFPWVR

PSPPQQRLPLLECTPQGTNLSTSNPLGFFPDHQLDPAFRANSANPDWDFNPNKDT WPDANKVGGQNLSTSNPLGFFPDHQLDPAF ANTANPDWTDF P DTWPDANK VG

SEO ID NO: 25 delta 4 wt

AGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCGCGAAGAAATTCTGGAA

CAGTGGGTGGGCGCGCGCAAAAAACTGGAAGAACTGGAACGCGATCTGCGC

AAAATTAAAAAAAAAATTAAAAAACTGGAAGAAGAAAACCCGTGGCTGGGC

AACATTAAAGGCATTCTGGGCAAAAAAGATCGCGAAGGCGAAGGCGCGCCG

CCGGCGAAACGCGCGCGCGCGGATCAGATGGAAGTGGATAGCGGCCCGCGC

AAACGCCCGTTTCGCGGCGAATTTACCGATAAAGAACGCCGCGATCATCGCC

GCCGCAAAGCGCTGGAAAACAAACGCAAACAGCTGAGCAGCGGCGGCAAAA

GCCTGAGCAAAGAAGAAGAAGAAGAACTGCGCAAACTGACCGAAGAAGATG

AACGCCGCGAACGCCGCGTGGCGGGCCCGCGCGTGGGCGGCGTGAACCCGCT

GGAAGGCGGCACCCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAG

GGCGTGCCGGAAAGCCCGTTTGCGCGCACCGGCGAAGGCCTGGATGTGCGCG

GCAACCAGGGCTTTCCGTGGGATATTCTGTTTCCGGCGGATCCGCCGTTTAGC

CCGCAGAGCTGCCGCCCGCAGGGCACCAACCTGAGCACCAGCAACCCGCTGG

GCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACAGCGCGAAC

CCGGATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAAG

TGGGCGGCCAGAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCAT

CAGCTGGATCCGGCGTTTCGCGCGAACACCGCGAACCCGGATTGGGATTTTA

ACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCGGAAGCGGAGCT

ACTAACT TCAGCCTGC TGAAGCAGGCTGGAGACGTGGAGGAGAACCCTGGACCTATGAG

CCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCGCGAAGAAGTGCTGGAACA

GTGGGTGAACGGCCGCAAAAAACTGGAAGAACTGGAACGCGAACTGCGCCG

CGCGCGCAAAAAAATTAAAAAACTGGAAGATGATAACCCGTGGCTGGGCAA

CGTGAAAGGCATTCTGGGCAAAAAAGATAAAGATGGCGAAGGCGCGCCGCC

GGCGAAACGCGCGCGCACCGATCAGATGGAAATTGATAGCGGCCCGCGCAA

.-\C <i ^' C i ^¾' i ^' CfC C} ^' C Ci ■< ^' I ^' i r.Xt 5 Λ ^' 1 ^' C 5 ί.Λ .-\C ^' < i ^' .\ 3 Λ FC ^' A I C < }C

CGCAAAGCGCTGAAAAACAAAAAAAAACAGCTGAGCGCGGGCGGCAAAAGC

CTGAGCAAAGAAGAAGAAGAAGAACTGAAACGCCTGACCCGCGAAGATGAA

GAACGCAAAAAAGAAGAACATGGCCCGAGCCGCCTGGGCGTGAACCCGAGC

GAAGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAGG

GCATTCCGGAAAGCCGCTTTACCCGCACCGGCGAAGGCCTGGATGTGCGCGG

CAGCCGCGGCTTTCCGCAGGATATTCTGTTTCCGAGCGATCCGCCGTTTAGCC

CGCAGAGCTGCCGCCCGCAGGGCACCAACCTGAGCACCAGCAACCCGCTGGG

CTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACAGCGCGAACC

CGGATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGT

GGGCGGCCAGAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCAT

CAGCTGGATCCGGCGTTTCGCGCGAACACCGCGAACCCGGATTGGGATTTTA

ACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCGGAAGCGGAGCT

ACTAACT TCAGCCTGCTGAAGCAGGCTGGAGACGTGGAGGAGAACCCTGGACCTATGAG

CCAGAGCGAAACCCGCCGCGGCCGCCGCGGCACCCGCGAAGAAACCCTGGA

AAAATGGATTACCGCGCGCAAAAAAGCGGAAGAACTGGAAAAAGATCTGCG

CAAAACCCGCAAAACCATTAAAAAACTGGAAGAAGAAAACCCGTGGCTGGG

CAACATTGTGGGCATTATTCGCAAAGGCAAAGATGGCGAAGGCGCGCCGCCG

GCGAAACGCCCGCGCACCGATCAGATGGAAGTGGATAGCGGCCCGGGCAAA

CGCCCGCATAAAAGCGGCTTTACCGATAAAGAACGCGAAGATCATCGCCGCC

GCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAGCGCGGGCGGCAAAATTC TGAGCAAAGAAGAAGAAGAAGAACTGCGCCGCCTGACCGATGAAGATGAAG AACGCAAACGCCGCGTGGCGGGCCCGCGCGTGGGCGATGTGAACCCGAGCCG

CGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGCAGATGGCGGGC

GTGCCGGAAAGCCCGTTTAGCCGCACCGGCGAAGGCCTGGATATTCGCGGCA

CCCAGGGCTTTCCGTGGGTGAGCCCGAGCCCGCCGCAGCAGCGCCTGCCGCT

GCTGGAATGCACCCCGCAGGGCACCAACCTGAGCACCAGCAACCCGCTGGGC

TTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACAGCGCGAACCC

GGATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTG

GGCGGCCAGAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATC ATC

AGCTGGATCCGGCGTTTCGCGCGAACACCGCGAACCCGGATTGGGATTTTAA

CCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCGGAAGCGGAGCTA

C T AAC T T C AG C C T G C T G AAG C AG G C T G GAGAC G T G GAG GAG AAC C C G GAG C T A TG AGC

CAGAGCGAAAGCAAAAAAAACCGCCGCGGCGGCCGCGAAGATATTCTGGAA

AAATGGATTACCACCCGCCGCAAAGCGGAAGAACTGGAAAAAGATCTGCGC

AAAGCGCGCAAAACCATTAAAAAACTGGAAGATGAAAACCCGTGGCTGGGC

AACATTATTGGCATTATTCGCAAAGGCAAAGATGGCGAAGGCGCGCCGCCGG

CGAAACGCCCGCGCACCGATCAGATGGAAATTGATAGCGGCACCGGCAAACG

CCCGCATAAAAGCGGCTTTACCGATAAAGAACGCGAAGATCATCGCCGCCGC

AAAGCGCTGGAAAACAAAAAAAAACAGCTGAGCAGCGGCGGCAAAAACCTG

AGCCGCGAAGAAGAAGAAGAACTGGGCCGCCTGACCGTGGAAGATGAAGAA

CGCCGCCGCCGCGTGGCGGGCCCGCGCACCGGCGATGTGAACCTGAGCGGCG

GCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGCGCATGGAAGGCGT

GCCGGAAAGCCCGTTTACCCGCACCGGCGAAGGCCTGGATATTCGCGGCAAC

CAGGGCTTTCCGTGGGTGCGCCCGAGCCCGCCGCAGCAGCGCCTGCCGCTGC

TGGAATGCACCCCGCAGGGCACCAACCTGAGCACCAGCAACCCGCTGGGCTT

TTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACAGCGCGAACCCGG

ATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGG

CGGCCAGAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGC

TGGATCCGGCGTTTCGCGCGAACACCGCGAACCCGGATTGGGATTTTAACCC

GAACAAAGATACCTGGCCGGATGCGAACAAAGTGGGC

SEQ ID NO: 26 delta 4 wt with restriction sites (Hindlll FxoRl)

A AGC T T GCACCATGGCCAGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCG

CGAAGAAATTCTGGAACAGTGGGTGGGCGCGCGCAAAAAACTGGAAGAACT

GGAACGCGATCTGCGCAAAATTAAAAAAAAAATTAAAAAACTGGAAGAAGA

AAACCCGTGGCTGGGCAACATTAAAGGCATTCTGGGCAAAAAAGATCGCGAA

GGCGAAGGCGCGCCGCCGGCGAAACGCGCGCGCGCGGATCAGATGGAAGTG

GATAGCGGCCCGCGCAAACGCCCGTTTCGCGGCGAATTTACCGATAAAGAAC

GCCGCGATCATCGCCGCCGC AAAGCGCTGGAAAACAAACGCAAACAGCTGA

GCAGCGGCGGCAAAAGCCTGAGCAAAGAAGAAGAAGAAGAACTGCGCAAAC

TGACCGAAGAAGATGAACGCCGCGAACGCCGCGTGGCGGGCCCGCGCGTGG

GCGGCGTGAACCCGCTGGAAGGCGGCACCCGCGGCGCGCCGGGCGGCGGCTT

TGTGCCGAGCATGCAGGGCGTGCCGGAAAGCCCGTTTGCGCGCACCGGCGAA

GGCCTGGATGTGCGCGGCAACCAGGGCTTTCCGTGGGATATTCTGTTTCCGGC

GGATCCGCCGTTTAGCCCGCAGAGCTGCCGCCCGCAGGGCACCAACCTGAGC

ACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCG

CGCGAACAGCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATACCTGG

CCGGATGCGAACAAAGTGGGCGGCCAGAACCTGAGCACCAGCAACCCGCTG

GGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACACCGCGAA CCCGGATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAA

GTGGGCGGAAGCGGAGCTACTAACT TCAGCCTGCTGAAGCAGGCTGGAGACGTGGAGGA

GAACCCTGGACCTATGAGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCGCG

AAGAAGTGCTGGAACAGTGGGTGAACGGCCGCAAAAAACTGGAAGAACTGG

AACGCGAACTGCGCCGCGCGCGCAAAAAAATTAAAAAACTGGAAGATGATA

ACCCGTGGCTGGGCAACGTGAAAGGCATTCTGGGCAAAAAAGATAAAGATGG

CGAAGGCGCGCCGCCGGCGAAACGCGCGCGCACCGATCAGATGGAAATTGAT

AGCGGCCCGCGCAAACGCCCGCTGCGCGGCGGCTTTACCGATCGCGAACGCC

AGGATCATCGCCGCCGCAAAGCGCTGAAAAACAAAAAAAAACAGCTGAGCG

CGGGCGGCAAAAGCCTGAGCAAAGAAGAAGAAGAAGAACTGAAACGCCTGA

CCCGCGAAGATGAAGAACGCAAAAAAGAAGAACATGGCCCGAGCCGCCTGG

GCGTGAACCCGAGCGAAGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGT

GCCGAGCATGCAGGGCATTCCGGAAAGCCGCTTTACCCGCACCGGCGAAGGC

CTGGATGTGCGCGGCAGCCGCGGCTTTCCGCAGGATATTCTGTTTCCGAGCGA

TCCGCCGTTTAGCCCGCAGAGCTGCCGCCCGCAGGGCACCAACCTGAGCACC

AGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGC

GAACAGCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATACCTGGCCG

GATGCGAACAAAGTGGGCGGCCAGAACCTGAGCACCAGCAACCCGCTGGGCT

TTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACACCGCGAACCCG

GATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGG

GCG GAAG CGGAGC TAG TAAC T T C AGCC T GC T GAAG CAGG C T G G AGA.C G T G G AG GAG AAC

CCTGGACCTATGAGCCAGAGCGAAACCCGCCGCGGCCGCCGCGGCACCCGCG

AAGAAACCCTGGAAAAATGGATTACCGCGCGCAAAAAAGCGGAAGAACTGG

AAAAAGATCTGCGCAAAACCCGCAAAACCATTAAAAAACTGGAAGAAGAAA

ACCCGTGGCTGGGCAACATTGTGGGCATTATTCGCAAAGGCAAAGATGGCGA

AGGCGCGCCGCCGGCGAAACGCCCGCGCACCGATCAGATGGAAGTGGATAG

CGGCCCGGGCAAACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACGCGAA

GATCATCGCCGCCGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAGCGCG

GGCGGCAAAATTCTGAGCAAAGAAGAAGAAGAAGAACTGCGCCGCCTGACC

GATGAAGATGAAGAACGCAAACGCCGCGTGGCGGGCCCGCGCGTGGGCGAT

GTGAACCCGAGCCGCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGC

CGCAGATGGCGGGCGTGCCGGAAAGCCCGTTTAGCCGCACCGGCGAAGGCCT

GGATATTCGCGGCACCCAGGGCTTTCCGTGGGTGAGCCCGAGCCCGCCGCAG

CAGCGCCTGCCGCTGCTGGAATGCACCCCGCAGGGCACCAACCTGAGCACCA

GCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCG

AACAGCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATACCTGGCCGG

ATGCGAACAAAGTGGGCGGCCAGAACCTGAGCACCAGCAACCCGCTGGGCTT

TTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACACCGCGAACCCGG

ATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGG

C G GAAG C G GAG C AC TAAC T T C AGCC GC T GAAGCAGGC T GGAGAC GT GGAGGAGAAC CC

TGGACCTATGAGCCAGAGCGAAAGCAAAAAAAACCGCCGCGGCGGCCGCGAA

GATATTCTGGAAAAATGGATTACCACCCGCCGCAAAGCGGAAGAACTGGAAA

AAGATCTGCGCAAAGCGCGCAAAACCATTAAAAAACTGGAAGATGAAAACC

CGTGGCTGGGCAACATTATTGGCATTATTCGCAAAGGCAAAGATGGCGAAGG

CGCGCCGCCGGCGAAACGCCCGCGCACCGATCAGATGGAAATTGATAGCGGC

ACCGGCAAACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACGCGAAGATC

ATCGCCGCCGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAGCAGCGGCG

GCAAAAACCTGAGCCGCGAAGAAGAAGAAGAACTGGGCCGCCTGACCGTGG

AAGATGAAGAACGCCGCCGCCGCGTGGCGGGCCCGCGCACCGGCGATGTGA AC rGAGCGGCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCrTTGKiCCGCG

CATGGAAGGCGTGCCGGAAAGCCCGTTTACCCGCACCGGCGAAGGCCTGGAT

ATTCGCGGCAACCAGGGCTTTCCGTGGGTGCGCCCGAGCCCGCCGCAGCAGC

GCCTGCCGCTGCTGGAATGCACCCCGCAGGGCACCAACCTGAGCACCAGCAA

CCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACA

GCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGC

GAACAAAGTGGGCGGCCAGAACCTGAGCACCAGCAACCCGCTGGGCTTTTTT

CCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACACCGCGAACCCGGATT

GGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCTG

AT GAGUAAT T CC G T

SEQ ID NO: 27 delta 4 codon optimized

G C C AG T C G GAG C GAAT C AAAGAAAAAT AG G G GAG GGC G G GAAGAAAT C C T G GAG C AG Τ G G G T C G GAG C AC GAAAGAAAC T G GAAG AAC G GAG AG G G AC C T G C G C AAGAT C AAGAAG AAG AT CAAGAAGC Τ GGAGGAGGAGAACCCC Τ GGC Τ GGGCAATAT CAAGGGCAT CC T GGGCAAG AAG GAT C G G GAG G GAGAG G GAG C AC C AC C T G C AAAGAG GGC C AGAG C C GAC C AGAT G GAG G T G GAT AG C G G C C C AG GAAG C G C C CAT T C AG AG G C GAG T T T AC AGAC AAG GAG C G GAGA G A T C AC AG G C G C C G GAAG G C C C T G G A G AAG AAG C G G A A G C AG C T G A G C T C C G G C G G C A AG T C C C T G T C AAG GAG GAG GAG GAG GAG C T GAGAAAG C T GAC C GAG GAG GAC GAGAGAAG G GAGAGGAGGGTGGCAGGACC TAGGGTGGGAGGCGTGAACCCACTGGAGGGAGGAACAAGG G GAG C AC C T G GAG GAG GAT T C G T G C CAT C CAT G C AG G GAG T G C C T GAG T C T C CAT T T G C C AG GAC C G GAGAG G G C C T G GAT G T G C G C G GAAA C AG G G C T T C C C C T G G GAC AT C C T G T T T C C T G C C G A T C C A C C C T T C T C C C C A C AG T C T T G C AG G C C AC AG G G AAC C AAC C T GAG C AC A T C C AAT CC T C T GGGC T T C T T T C C AGAC C AC C AG C T G GAT C C T G C C T T C AGAG C C AAC T C C G C C AAT C C AG AC T G G GAC T T C AAC C C C AAT AG GAC AC AT G G C C T GAT G C C AAC AG G T C G G C G G C C AGAAC C T G T C T AC C AG C AAT CCCC T GGGC T T C T T T CC GAC C AC C AG C T G GAT C C AG C C T T C C G G G C C AAC AC T G C T AC C C T GAT T G G GAC T T C AAC C C T A AAG GAT AC C T G G C C A GAC G C C A A C AAG G T C G G C G GAAG C G GAG C TAG AAC T T C A G C C T G C T GAAG C G G C T G GAGAC G T G GAG GAGAAC C C T G GAC C T AT G T C C AG G T C T GAGAG C AAGAAGAAT AG G G GAG GAAG AG AG GAG G T G C T G GAG C AG T G G G T G AAC G G C C G C AAG AAG C T G GAG GAG C T G G A GAG G GAG C T GAG AAG G G C C C G C A A GAAG AT C A AG A A G C T G GAAG AC G A T AAT C C T T G G C T G G G C AT G T GAAAG G CAT C C T G G G C AAGAAG GAC AAG GAT G GAGAG G GAG C AC C T C C A G C A A AG AG G G C A AG A A C AG A C C AG AT G GAG AT C GAT T C T G GAC C AAG GAAG C G C C C T C T G AG G G GAG G C T T C AC C GAC C G G GAGAG AC AG GAT C AC C G C C G GAGAAAG G C C C T G AAGAAC AAG AAG AG C AG C T G T C C G C C G G C G G C AAG T C C C T GAG C AAAG AAG AG GAAG AG GAG C T G AAGAGGCTGACCCGCGAGGACGAGGAGCGGAAGAAGGAGGAGCACGGACCAAGCAGACTG G GAG T GAAT C C T T C C GAG G GAG GAC C AAGAG GAG C AC C C G GAG GAG G C T T C G T G C CAT C T AT G C AG G G CAT C C C C GAGAG C C G G T T TAG C AGAAC AG GAGAG G G C C T G GAC G T GAG G G G C T CCCGCGGC T T T CC C AG GAC AT C C T G T T C C C AT C T GAT CCCCC T T TAG C C C AC AG C C T G TAG G C C C C AG G G C AC T AAC C T GAG C AC AT C C AAC C C AC T GGGC T T C T T T C C T GAT CAT C A G C T G GAC C C AG C C T T C C G C G C C A A C AG C G C C A AC C C T GAC T G G GAC T T C AAC C C A A AT AAG GAC AC AT GGC C AG A G C T AAC AAG G T C G GAG GAC AAAAC C T G T C TAG C AG C AAC C C T C T G G G C T T C T T T C C C GAT CAT C AG C T G GAC C C C G C C T T C AG G G C C AAC AC AG C C AA C C C GAC T GGGAC T T CAACCCGAATAAGGACACC T GGC CAGAT GCAAACAAGGT CGGAGGAAGC G GAG C T AC T AAC T T C AG C C T G C T GAAG C AG G C T G GAGAC G T G GAG GAGAAC C C T G GAC C T AT GAG C C AG T C T GAGAC AAG GAG G G G C C G GAGAG GAAC C AG G GAG GAGAC AC T G GAG AAG T G GAT C AC C G C GAGAAAG AAG G C C G A G GAG C T G GAG A A G GAC C T G C G G A A GAC C AG A A AG AC AAT C AAGAAG C T G GAAGAAGAGAAC C CAT G G C T G G G C AAT AT C G T G G G CAT CAT C C G C AAGGGCAAGGAC GGCGAGGGAGCACCAC CAGCAAAGAGGC CCCGCACAGAT CAGAT GGAA G T G GAT AG C G G C C C T G G C AAGAG G C C AC AC AAG T CCGGC T T C AC C GAC AAG GAGAG G GAG GAC CAT AG G C G C C G GAAG G C C C T G GAAAAC AGAAGAAG C AA TAT C C G C C G G C G G C AAG AT C C T G C C AAA GAG GAAG A AG AG GAG C T GAG A AG G C T G A C C G A C GAG GAT GAG G A GAG G AAAAGAAGGGTGGCAGGACCAAGAGTGGGCGACGTGAATCCCAGCAGAGGCGGACCAAGA G GAG C AC C T G GAG G C G G C T T C G T G C C C C AGAT G G C C G G C G T G C C C GAG TCTCCT T T TAG C AGAACTGGAGAGGGCC GGATATCAGGGGAACACAGGGCT TCCATGGGTGAGCCCATCC C

C T C C AC AG GAG AG G C T G C C AC T G C G GAG T G C AC C C C T C AG G G AAC C AAC C T G T C TAG C A G C A A C C C G C T G G G C T C T T T C C C G AC C A T C AG C T G G AC C C T G C C T T C C G C G C C AAC C C G C C AC C C T GAT T G G GAC T T C AAC C C GAAT AAG GAT AC C T G G C C C GAC G C T AC AAG G T C G GAG G C C AGAAC C T G T C C AC C T C AAC C C C T TAG GCT TCT T TCCC GAT C AC C AG C T G GAT C C C G C C T T C GAG C C AAC AC T G C T AAC C C C GAT T G G GAC T T C AAC C C GAAT AAG GAC AC G T G G C C AGAC G C T AAC AG G T C G G G G GAAG C G GAG C T AC T AC T T C AG C C T G C T GAAG C AG G C T G GAG AC G T G GAG GAGAAC C C T G GAC C T A T G T C G C AG T C C GAG T C TAAGAAGAATAGAA G G G G C G G C C G G GAG GA T AT C C T G G AAAAT G GAT C AC C AC AC G C AGAAAAG C T GAAG AAC T G GAAAAG GAC C T GAG GAAG G C C C G C AAG AC CAT C AAGAAG C T G GAG GAT GAAAAT C CAT G G C T G G G AAA CAT CAT C G G CAT CAT C AGAAAG G G C AAG GAC G G G GAAG G C G C C C C AC C T G C AAAG C G G C C T AGAAC C GAT C AGAT G GAAAT C GAT T C T G G C AC AG G C AAG C G G C C AC AC A AGAG T G G C T T C AC C GA AAG G AGAG AGAG GAT C AC AG AAG G C G C AAG G C C C T G GAGAAC A AG AAGAAG C AAT T AAG C AG C G G C G G C AAGAAT C T G T C C GAG AGAAGAG GAG GAG C T G G G C AG AC T GAC AG T G GAG GAC GAG GAG C G GAG AAG G C G C G T G G C AG GAC C AAG GAC C G G C G AT G T G AAC C T G A G C G GAG G A G GAC C TAG G G G A G C AC C AG GAG G C G G C T T C G T G C C T AG G A T G GAG G GAG T G C C A GAG T C C C C C T T T AC C A G GAC T G G C GAG G G C C T G GAC AT C A G G G G ΑΆ AT C AG G GAT T C C CAT G G G T G C G G C C TAG C C C AC C AC AG C AGAG AC T G C C AC T G C T G GAG T GTACACCCCAGGGCACAAAGCTGAGCACATCCAATCCGCTGGGC T TCT T TCCAGATCATC AAT T AGAT C C AG C C T T C AG G G C C AAC T C C G C C AAT C C G GAT T G G GAC T T C AC C C GAAT A AG GAC AC T T G G C C C GAC G C AAAC AAG G T C G GAG G G C AAAAC C T G T C T AC C AG C AAT C C AC T TGGCT TCT T TCCTGACCATCAGCTGGATCCCGCCT T TCGCGCCAATACCGCCAATCCTG AC T G G GAC T T C AAT C C T AAC AAAGAC AC C T G G C C C GAC G C AAAC AAAG T G G GA

SEQ ID NO: 28 delta 4 optimized with restriction sites (HindlH /EcoRI)

A AGC T T GCA CCATGGCCAGT C GGAGCGAAT CAAAGAAAAATAGGGGAGGGCGGGAAGAA ATCCTGG AG C AG T G G G T C G GAG C AC G AAAG AAAC T G GAAG AAC T G GAG AG G GAC C T G C G C A AG A T C A A GAAG AAG T C A A GAAG C T G GAG G A G GAGAAC C C C G G C G G G C A AT AT C AAG G G CAT C C T G G G C AAGAAG GAT C G G GAG G GAGAG G GAG C AC C AC C T G C AAAGAG G G C C AGA G C C GAC C AGAT G GAG G T G GA AG C G G C C C TAG GAAG C G C C CAT T C AG AG G C GAG T T AC A GACAAGGAGCGGAGAGATCACAGGCGCCGGAAGGCCCTGGAGAACAAGCGGAAGCAGCTG AG C T C C G G C G G C AAG TCCCTGTC T AAG GAG GAG GAG GAG GAG C T GAGAAAG C T GAC C GAG G A G GAC GAGA GAAG G GAGAG G A G G G T G G C A G GAC C TAG G G G G GAG G C G T G AAC C C AC T G GAG G GAG G AAC AAG G G GAG C AC C T G GAG GAG GAT T C G T G C CAT C CAT G C AG G GAG G C C T GAG T C T C CAT T T G C C AG GAC C G GAGAG G G C C T G GAT G T G C G C G GAAAT C AG G G C T T C C C C T G G GAC AT C C T G T T C C T G C C GAT C C AC C C T T C T C C C C AC AG T C T G C AG G C C AC AG G G A AC C AAC C T GAG C AC AT C C AAT CCTCTGGGCT TCT T TC C AGAC C AC C AG C T G GzAT C C T G C C T T C AG AG C C AAC T C C G C C AA C C AG AC T G G GAC T T C AAC C C C AA AAG GAC AC AT G G C C T GA T G C C AAC AAG G T C G G C G G C C AGAAC C T G T C C C AG C AAT CCCCTGGGCT TCT T TCCT GAC C AC C AG C T G GAT C C AG CCT TCCGGGC C AAC AC T G C T AAC C C T GAT T G G GAC T T C AAC CCTAATAAGGATACCTGGCCAGACGCCAACAAGGTCGGCGGAAGCGGAGCTACTAACT TC AG C C T G C GAAG C A G G C T G GAG AC G T G GAG GAGAAC C C T G G A C C T A T G T C C AG G T C T GAG AG C AAGAAGAAT AG G G GAG GAAG AGAG GAG G T G C T G GAG C AG T G G G T GAAC G G C C G C AAG AAG C T G G A G GAG C T G GAGAG G GAG C T G A GAAG G G C C C G C AG A GAT C AAGAAG C T G G A A GAC GAT AT CCT TGGCTGGG C AAT G T GAAAG G CAT C C T G G G C AGAAG GAC AAG GAT G GA GAG G GAG C AC C T C C AG C AAAGAG G G C AAGAAC AGAC C AG AT G G AGAT C GAT T C T G GAC C A AGGAAGCGCCCTCTGAGGGGAGGCT TCACCGACCGGGAGAGACAGGATCACCGCCGGAGA AAG G C C C T GAAG AAC AAG AG AAG C AG C T G T C C G C C G G C G G C AAG T C C C T GAG C AAG A GAGGAAGAGGAGCTGAAGAGGC TGACCCGCGAGGACGAGGAGCGGAAGAAGGAGGAGCAC G GAC C AAG C AG A C T G G GAG T G A C C T T C C G A G G G A G GAC C AAG AG G A G C AC C C G GAG G A GGCTTCGTGC CAT C T AT G C AG G G CAT C C C C GAG G C C G G AG C AGAAC AG G GAG G G C C T G GAC G T GAG G G G C T C C CGCGGCTTTCCT C AG GAC AT C C T G T T C C CAT C T GAT C C C C C T T AGCCCACAGTCCTGTAGGCCCCAGGGCAC AACCTGAGCACATCCAACCCACTGGGC TTCTTTCCT GAT C A T C AG C T G GAC C C AG CCTTCCGCGC C AAC AG C G C C AAC C C T GAC T G G GAC T T C AAC C C AAAT AAG GAC AC AT G G C C AG AT G C T AAC AAG G T C G GAG GAC AAAA.C C T G T C T C C AG C AAC C C T C T G G G C T T C T T T C C C G T CAT C AG C T G G C C C C G C C T T C AG G G C C AAC AC AG C C AAT C C C GAC T G G GAC T T C AAC C C GAAT AAG GAC AC C T G G C C AGAT G C AAAC AAG G T C G GAG G AAG C G GAG C AC T AAC T T C AG C C T G C T G AAG C AG G C T G GAGAC G T G GAG GAG AC C C T G G C C T T GAG C C AG T C T GAG AC AAG GAG G G G C C G GAG G G A C C AG G GAG GAGAC AC T G GAGAAG T G GAT C AC C G C C AGAAAGAAG G C C GAG GAG C T G GAG AAG GAC C T G CGGAAGACCAGAAAGACAATCAAGAAGCTGGAAGAAGAGAACCCATGGCTGGGCAATATC G T G G G CAT CAT C C G C AG G G C AAG GAC G G C G G G G G C AC C AC C AG C A AAG G G C C C C G C AC AGAT C AG AT G G AAG T G GAT AG C G G C C C T G G C AAGAG G C C AC AC AAG T C C G G C T T C AC C GACAAGGAGAGGGAGGACCATAGGCGCCGGAAGGCCCTGGAPAACAAGAAGAAGCAATTA TCCGCCGGCGGCAAGATCCTGTCCAAAGAGGAAGAAGAGGAGCTGAGAAGGCTGACCGAC GAG GAT GAG GAGAG GAAAAGAAG G G T G G C AG GAC C AAGAG T G G G C GAC G T GAAT C C C AG C AG AG G C G GAC C AAG AG G A G C AC C T G GAG GCGGCTTCG G C C C C AG A T G G C C G GCGTGCCC GAG TCTCCTTT TAG C AGAAC T G GAGAG G G C C T G GAT AT C AG G G GAAC AC AG G G C T T T C C A TGGGTGAGCCCATCCC

C T C C AC AG C AGAG G C T G C C AC T G C T G GAG T G C AC C C C C AG G G AC C AAC C T G T C T AC C A G C AAC C C G C T G G G C T T C T T T C C C GAC CAT C AG C T G GAC C C T G C C T T C C G C G C CMC T C C G CCAACCCTGATTGGGACTTCAACCCGAATAA.GGATACCTGGCCCGACGCTAACAA.GGT CG GAG G C C AGAAC C T G T C C AC C T C T AAC C C C T TAG GCTTCTTTCCC GAT C AC C AG C T G GAT C C C G C C T T C AGAG C CAACAC T G C AAC C C C GAT T G G GAC T T C AAC C C GAAT AAG GAC AC G T G G C C AGAC G C T AC AAG G T C G G G G G AAG C G GAG C AC T AAC T T C AG C C T G C T G AAG C AG G C T G GAGAC G T G GAG GAG AAC C C T G GAC C T AT G T C G C AG T C C GAG T C T AAGAAGAAT AGAA G G G G C G G C C G G GAG GAT T C C T G GAAAAAT G GAT C AC C AC AC G C AG AAAAG C G AAGAAC T G GAAAAG GAC C T GAG G AAG G C C C G C A GAC CAT C AAGAAG C T G GAG GAT GAAAAT C CAT G G C T G G GAAAC AT CAT C G G CAT CAT C AGAAAG G G C AAG GAC G G G G AAG G C G C C C C AC C T G C A AG C G G C C TAG AC C GAT C A GAT G G AAA T C G A T T C T G G C A C AG G C AAG C G G C C AC A C A AGAG T G G C T T C AC C GAT AAG GAGAGAGAG GAT C AC AG AAG G C G C AAG G C C C T G GAGAAC A AGAAG AAG C AAT AAG C AG C G G C G G C AAG AAT C T G T C CAGAGAAG AAGAG GAG GAG C T G G GCAGACTGACAGTGGAGGACGAGGAGCGGAGAAGGCGCGTGGCAGGACCAAGGACCGGCG Z T G T G AC C T GAG C G GAG GAG GAC C TAG G G GAG C AC C AG GAG GCGGCTTCGTG C C TAG GA T G G A G G G A G T G C C AG A G T C C C C C T T TAG C AG GAC G G C G A G G G C C T G GAC AT C AG G G G A A AT C AG G GAT T C C C T G G G T G C G G C C T AG C C C AC C AC AG C AG A GAC T G C C A C T G C G G A G T G TAG AC C C C AG G G C AC AAAC C T GAG C AC AT C C AA C C G C T G G G C T T C T T T C C AGAT CA C AAT T AGAT C C AG C C T C AG G G C C AAC C C G C C AA C C G GA T T G G GAC T T C AAC C C GAAT A AG GAC AC T T G G C C C GAC G C AAAC AAG G T C G GAG G G C AAAAC C T G T C TAG C AG C AAT C C AC T T G G C T T C T T T C C T GAC CAT C AG C T G GA C C C G C C T T T C G C G C C AA AC C G C C AAT C C T G AC T G G GAC T T C AAT C C T AAC AAAGAC AC C T G G C C C GAC G C AAAC AAAG T G G GATGAT GAG AATTCCGT

SEQ ID NO: 29 delta 4 protein

MASRSESKKNRGGREEILEQWVGARKKLEELERDLRKIKKKIKKLEEENPWLGNI

KGILGKKDREGEGAPPAKRARADQMEAOSGPRKRPFRGEFTDKERRDHRRRK AL

EN RKQLSSGGKSLSKEEEEELR LTEEDERRERRVAGPRVGGVNPLEGGTRGAP

GGGFVPSMQG\ ESPFARTGEGLDVIIGNQGFPWDILFPADPPFSPQSCRI ^> QGTNL

STSNPLGFFPDHQLDPAFRANSANPDWDFNPN DTWPDANKVGGQNLSTSNPLG

FFPDHQLDPAFRANTANPDWDFNPNKDTWPDANKVGGSGATNFSLLKQAGDVE

ENPGPMSRSESKKNRGGREEVLEQWVNGRK LEELERELRRAR KIKKLEDDNP

WLGNVKG1LGKKDKDGEGAPPA RARTDQMEIDSGPRKRPLRGGFTDRERQDH RRRKALKNKKKQLSAGGKSLSKEEEEELKRLTREDEERK EEHGPSRLGVNPSEG GPRGAPGGGFVPSMQGIPESRFTRTGEGLDVRGSRGFPQDILFPSDPPFSPQSCRPQ

GT .STS PLGFFPDHQLDPAFRA SA PDWDFNPNKDTWPDA KVGGQ LSTS

NPLGFFPDHQLDP AFRANTANPDWDFNPNKDTWPD ANKVGG SG ATNF SLLKQ A

GDVEENPGPMSQSETRRGRRGTREETLEKWITARKKAEELE DLRKTRKTIKKLE

EENPWLG iVGIIli G DGEGAPPAKRI'RTDQMEVDSGPGKRPH SGFTDKEi ED

HPvRRXALE KKKQLSAGGKILSKEEEEELRRLTDEDEERKRRVAGPRVGDVNPS

RGGPRGAPGGGFVPQMAGVPESPFSRTGEGLDIRGTQGFPWVSPSPPQQRLPLLE

CTP( 5 NLSTSNPLGFFPDH:QLDPAF:RA SANPDWD]^PNKDT\VP[)ANKVXKJ-Q

NLSTSNPLGFFPDHQLDPAFRANTANPDVVDFNPNKDTWPDA VGGSGATNFSL

LKQAGD\¾E PGPMSQSESKK1\¾RGGREDILEKWITTRRKAEELEKDLRKARKTI

KKLEDENPWLGNIIGnRKGKDGEGAPPAKRPRTDQMEIDSGTGKRPHKSGFTDKE

REDHRRRKALENK KQLSSGGKNLSREEEEELGRLTVEDEERRRRVAGPRTGDV LSGGGPRGAPGGGFWRMEGVPESPFTRTGEGLDIRGNQGFPWVRPSPPQQRLP

LLECTPQGT LSTS PLGFFPDHQLDPAFRANSA PDWDF P KDTWPDA VG

GQNLSTSNPLGFFPDHQLDPAFRANTANPDWDFNP DTWPDA KVG

SEQ ID NO: 30 delta 5 wt

AGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCGCGAAGAAATTCTGGAA

CAGTGGGTGGGCGCGCGCAAAAAACTGGAAGAACTGGAACGCGATCTGCGC

AAAATTAAAAAAAAAATTAAAAAACTGGAAGAAGAAAACCCGTGGCTGGGC

AACATTAAAGGCATTCTGGGCAAAAAAGATCGCGAAGGCGAAGGCGCGCCG

CCGGCGAAACGCGCGCGCGCGGATCAGATGGAAGTGGATAGCGGCCCGCGC

AAACGCCCGTTTCGCGGCGAATTTACCGATAAAGAACGCCGCGATCATCGCC

GCCGCAAAGCGCTGGAAAACAAACGCAAACAGCTGAGCAGCGGCGGCAAAA

GCCTGAGCAAAGAAGAAGAAGAAGAACTGCGCAAACTGACCGAAGAAGATG

AACGCCGCGAACGCCGCGTGGCGGGCCCGCGCGTGGGCGGCGTGAACCCGCT

GGAAGGCGGCACCCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAG

GGCGTGCCGGAAAGCCCGTTTGCGCGCACCGGCGAAGGCCTGGATGTGCGCG

GCAACCAGGGCTTTCCGTGGGATATTCTGTTTCCGGCGGATCCGCCGTTTAGC

CCGCAGAGCTGCCGCCCGCAGAGCCGCAGCGAAAGCAAAAAAAACCGCGGC

GGCCGCGAAGAAGTGCTGGAACAGTGGGTGAACGGCCGCAAAAAACTGGAA

GAACTGGAACGCGAACTGCGCCGCGCGCGCAAAAAAATTAAAAAACTGGAA

GATGATAACCCGTGGCTGGGCAACGTGAAAGGCATTCTGGGCAAAAAAGATA

AAGATGGCGAAGGCGCGCCGCCGGCGAAACGCGCGCGCACCGATCAGATGG

AAATTGATAGCGGCCCGCGCAAACGCCCGCTGCGCGGCGGCTTTACCGATCG

CGAACGCCAGGATCATCGCCGCCGCAAAGCGCTGAAAAACAAAAAAAAACA

GCTGAGCGCGGGCGGCAAAAGCCTGAGCAAAGAAGAAGAAGAAGAACTGAA

ACGCCTGACCCGCGAAGATGAAGAACGCAAAAAAGAAGAACATGGCCCGAG

CCGCCTGGGCGTGAACCCGAGCGAAGGCGGCCCGCGCGGCGCGCCGGGCGG

CGGCTTTGTGCCGAGCATGCAGGGCATTCCGGAAAGCCGCTTTACCCGCACC

GGCGAAGGCCTGGATGTGCGCGGCAGCCGCGGCTTTCCGCAGGATATTCTGT

TTCCGAGCGATCCGCCGTTTAGCCCGCAGAGCTGCCGCCCGCAGGGAAGCGGAG

C TAG T AAC T T GAG C C T G C T GAAG C AG G C T G GAG AC G T G GAG GAGAAC C C T G GAG C T ATG

AGCCAGAGCGAAACCCGCCGCGGCCGCCGCGGCACCCGCGAAGAAACCCTG

GAAAAATGGATTACCGCGCGCAAAAAAGCGGAAGAACTGGAAAAAGATCTG

CGCAAAACCCGCAAAACCATTAAAAAACTGGAAGAAGAAAACCCGTGGCTG

GGCAACATTGTGGGCATTATTCGCAAAGGCAAAGATGGCGAAGGCGCGCCGC

CGGCGAAACGCCCGCGCACCGATCAGATGGAAGTGGATAGCGGCCCGGGCA AACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACGCGAAGATCATCGCCG

CCGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAGCGCGGGCGGCAAAAT

TC TGAGC AAAGAAG AAGAAG AAGAACTGCGC CGCC TGAC CGATGAAGATGA

AGAACGCAAACGCCGCGTGGCGGGCCCGCGCGTGGGCGATGTGAACCCGAG

CCGCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGCAGATGGCG

GGCGTGCCGGAAAGCCCGTTTAGCCGCACCGGCGAAGGCCTGGATATTCGCG

GCACCCAGGGCTTTCCGTGGGTGAGCCCGAGCCCGCCGCAGCAGCGCCTGCC

GCTGCTGGAATGCACCCCGCAGAGCCAGAGCGAAAGCAAAAAAAACCGCCG

CGGCGGCCGCGAAGATATTCTGGAAAAATGGATTACCACCCGCCGCAAAGCG

GAAGAACTGGAAAAAGATCTGCGCAAAGCGCGCAAAACCATTAAAAAACTG

GAAGATGAAAACCCGTGGCTGGGCAACATTATTGGCATTATTCGCAAAGGCA

AAGATGGCGAAGGCGCGCCGCCGGCGAAACGCCCGCGCACCGATCAGATGG

AAATTGATAGCGGCACCGGCAAACGCCCGCATAAAAGCGGCTTTACCGATAA

AGAACGCGAAGATCATCGCCGCCGCAAAGCGCTGGAAAACAAAAAAAAACA

GCTGAGCAGCGGCGGCAAAAACCTGAGCCGCGAAGAAGAAGAAGAACTGGG

CCGCCTGACCGTGGAAGATGAAGAACGCCGCCGCCGCGTGGCGGGCCCGCGC

ACCGGCGATGTGAACCTGAGCGGCGGCGGCCCGCGCGGCGCGCCGGGCGGC

GGCTTTGTGCCGCGCATGGAAGGCGTGCCGGAAAGCCCGTTTACCCGCACCG

GCGAAGGCCTGGATATTCGCGGCAACCAGGGCTTTCCGTGGGTGCGCCCGAG

CCCGCCGCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCGCAG

SEQ ID NO: 31 delta 5 wt with restriction sites (Hindlll /EcoRI)

A AGC T T GCACCATGGCCAGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCG

CGAAGAAATTCTGGAACAGTGGGTGGGCGCGCGCAAAAAACTGGAAGAACT

GGAACGCGATCTGCGCAAAATTAAAAAAAAAATTAAAAAACTGGAAGAAGA

AAACCCGTGGCTGGGCAACATTAAAGGCATTCTGGGCAAAAAAGATCGCGAA

GGCGAAGGCGCGCCGCCGGCGAAACGCGCGCGCGCGGATCAGATGGAAGTG

GATAGCGGCCCGCGCAAACGCCCGTTTCGCGGCGAATTTACCGATAAAGAAC

GCCGCGATCATCGCCGCCGCAAAGCGCTGGAAAACAAACGCAAACAGCTGA

GCAGCGGCGGCAAAAGCCTGAGCAAAGAAGAAGAAGAAGAACTGCGCAAAC

TGACCGAAGAAGATGAACGCCGCGAACGCCGCGTGGCGGGCCCGCGCGTGG

GCGGCGTGAACCCGCTGGAAGGCGGCACCCGCGGCGCGCCGGGCGGCGGCTT

TGTGCCGAGCATGCAGGGCGTGCCGGAAAGCCCGTTTGCGCGCACCGGCGAA

GGCCTGGATGTGCGCGGCAACCAGGGCTTTCCGTGGGATATTCTGTTTCCGGC

GGATCCGCCGTTTAGCCCGCAGAGCTGCCGCCCGCAGAGCCGCAGCGAAAGC

AAAAAAAACCGCGGCGGCCGCGAAGAAGTGCTGGAACAGTGGGTGAACGGC

CGCAAAAAACTGGAAGAACTGGAACGCGAACTGCGCCGCGCGCGCAAAAAA

ATTAAAAAACTGGAAGATGATAACCCGTGGCTGGGCAACGTGAAAGGCATTC

TGGGCAAAAAAGATAAAGATGGCGAAGGCGCGCCGCCGGCGAAACGCGCGC

GCACCGATCAGATGGAAATTGATAGCGGCCCGCGCAAACGCCCGCTGCGCGG

CGGCTTTACCGATCGCGAACGCCAGGATCATCGCCGCCGCAAAGCGCTGAAA

AACAAAAAAAAACAGCTGAGCGCGGGCGGCAAAAGCCTGAGCAAAGAAGAA

GAAGAAGAACTGAAACGCCTGACCCGCGAAGATGAAGAACGCAAAAAAGAA

GAACATGGCCCGAGCCGCCTGGGCGTGAACCCGAGCGAAGGCGGCCCGCGC

GGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAGGGCATTCCGGAAAGCC

GCTTTACCCGCACCGGCGAAGGCCTGGATGTGCGCGGCAGCCGCGGCTTTCC

GCAGGATATTCTGTTTCCGAGCGATCCGCCGTTTAGCCCGCAGAGCTGCCGCC

CGCAGGGAAGCGGAGCTACTAACTTCAGCCTGCTGAAGCAGGCTGGAGACGTGGAGG AG AACCC T GGAC C TATGAGCCAGAGCGAAACCCGCCGCGGCCGCCGCGGCACCCG CGAAGAAACCCTGGAAAAATGGATTACCGCGCGCAAAAAAGCGGAAGAACT

GGAAAAAGATCTGCGCAAAACCCGCAAAACCATTAAAAAACTGGAAGAAGA

AAACCCGTGGCTGGGCAACATTGTGGGCATTATTCGCAAAGGCAAAGATGGC

GAAGGCGCGCCGCCGGCGAAACGCCCGCGCACCGATCAGATGGAAGTGGAT

AGCGGCCCGGGCAAACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACGCG

AAGATCATCGCCGCCGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAGCG

CGGGCGGCAAAATTCTGAGCAAAGAAGAAGAAGAAGAACTGCGCCGCCTGA

CCGATGAAGATGAAGAACGCAAACGCCGCGTGGCGGGCCCGCGCGTGGGCG

ATGTGAACCCGAGCCGCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGT

GCCGCAGATGGCGGGCGTGCCGGAAAGCCCGTTTAGCCGCACCGGCGAAGGC

CTGGATATTCGCGGCACCCAGGGCTTTCCGTGGGTGAGCCCGAGCCCGCCGC

AGCAGCGCCTGCCGCTGCTGGAATGCACCCCGCAGAGCCAGAGCGAAAGCAA

AAAAAACCGCCGCGGCGGCCGCGAAGATATTCTGGAAAAATGGATTACCACC

CGCCGCAAAGCGGAAGAACTGGAAAAAGATCTGCGCAAAGCGCGCAAAACC

ATTAAAAAACTGGAAGATGAAAACCCGTGGCTGGGCAACATTATTGGCATTA

TTCGCAAAGGCAAAGATGGCGAAGGCGCGCCGCCGGCGAAACGCCCGCGCA

CCGATCAGATGGAAATTGATAGCGGCACCGGCAAACGCCCGCATAAAAGCGG

CTTTACCGATAAAGAACGCGAAGATCATCGCCGCCGCAAAGCGCTGGAAAAC

AAAAAAAAACAGCTGAGCAGCGGCGGCAAAAACCTGAGCCGCGAAGAAGAA

GAAGAACTGGGCCGCCTGACCGTGGAAGATGAAGAACGCCGCCGCCGCGTG

GCGGGCCCGCGCACCGGCGATGTGAACCTGAGCGGCGGCGGCCCGCGCGGCG

CGCCGGGCGGCGGCTTTGTGCCGCGCATGGAAGGCGTGCCGGAAAGCCCGTT

TACCCGCACCGGCGAAGGCCTGGATATTCGCGGCAACCAGGGCTTTCCGTGG

GTGCGCCCGAGCCCGCCGCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCGC

AGTGAT GAGUAATTCC G T

SEQ ID NO: 32 delta 5 codon optimized

G C C T C A C G G T C AG A G T C AAAG AAAAA TAG G G G G G G G C G G G A A G AAA T C C T G G A A C AG T G G G T C G GAG C AC G G AAAAAAC G G A GAG C T G G A GAG G GAG C T G C G C AG C A AG A G AG AT C AAGAAG C G GAG GAG GAG AAC C C C T G G C T G G G C A A C AG G G CAT C C T G G G C AAG A A G GAT C G G G G G G G AG G GAG C AC C C C T G C AAAG AG G G C C G AG C C G A C C AG T G G G G T G GAT AG C G G C C C TAG GAAG C G C C CAT T C AGAG G C GAG T T T AC C GAC AG GAG C G GAGA GAT C AC AG G C G C C G GAAG G C C C G G AGAAC AG C G GAAG C AG C T GAG C T C C G G C G G C AAG TCCCTGTC T A AG G A G GAG GAG GAG G A G C T GAGAAAGC T GACAGAGGAGGACGAGAGAAGG GAG CGCCGGGTGG C C G G C C C AAG GGTGGGCGGCGT G AAC C C C C T G GAG G GAG G AAC C AG G G GAG C AC C T G GAG GAG G C T C G G C CAT C TAT G C AG G G C G T G C C T GAG G C C CAT T T G C C AG GAC AG GAG AG G G C C T G GAT G T G C G C G G C AAT C AG GGCTTCCCCTGG GAC AT C C T G T T T C C T G C C GAT C C AC C C T T C AG C C C AC AG T C C T G C AG G C C T C AGAG C AG AT C C GAG T C T AAG AAGAACAGGGGAGGAAGAGAGGAGGTGCTGGAGCAGTGGGTGAATGGCCGGAAGAAGCTG GAG GAG C T G GAG C G G GAG C T GAGAAGGGCCAGAAAGAAGAT C AGAAG C T GGAAGACGAT AAT C C T T G G C T G G G C AAT G T GAAAG G CAT C C T G G G C AG AAG GAC AAG GAT G GAG AG G G A GCACCTCCAGCAAAGAGGGCAAGAACCGACCAGATGGAGATCGATAGCGGACCAAGGAAG C G C C C T C T GAGAG GAG G C T T C AC AGAC C G G GAGAGAC AG GAT C AC C G C C G GAGAAAG G C C C T G AG AAC AAG AA G AG C AG C T G T C C G C C G GAG G C A A GAG C C T G T C C AAAG AA GAG G . A GAGGAGCTGAAGAGGCTGACCCGCGAGGACGAGGAGCGGAAGAAGGAGGAGCACGGCCCT T C C AG AC T G G G C G T GMT C CAT C T GAG G GAG GAC C AAG G G GAG C AC C AG G C G G C G G C T T C G T G C C AG C A T G C A G G G C T C C C C G A G T C C C G G T T T AC C AG AC AG GAGA G G G C C T G G C G T GAG G G G C T C T C G C G G C T T T C C T C AG GAC AT CCTGTTCC C AAG C GAT CCCCCTTTTTCT C C AC AGAG C T G T C G C C C C C AG G GAAG C G GAG C T AC T AC T T C AG C C G C T GAAG C AG G C T GGAGACGTGGAGGAGAACCCTGGACCTATGTCTCAGAGCGAGACAAGGAGGGGCCGGAGA G GAAC C AG G GAG GAGAC AC T G GAGAAG T G GAT C AC AG C C AGAAAGAAG G C C GAG GAG C T G GAGAAGGACC T GCGGAAGACCAGAAAGACAAT CAAGAAGC T G GAAG AAGAAAAT C CAT GG C T G G GAAAT AT C G T G G G CAT CAT C AG GAAG G G C AAG GAG G G C GAG G GAG C AC C AC C AG C C A AG A G G C C T C G C AC T GAT C A GAT G GAG G T G G A T T C C G G C C C T G G C AAG AG G C C AC A C AG TCTGGCTTCACAGACAAGGAGAGGGAGGACCATAGGCGCCGGAAGGCCCTGGAAAACAAG AAG AAG C AAT TAT C T G C C G G C G G C AAG AT C C T GAG C AAAGAG G AAGAG GAG GAG C T GAGA AG G C T G AC C G AC GAG GAT G A G GAG AG GAAG AG GAG G G T G G C AG G AC C A AG AG T G G G C G AC G T GAAT C C TAG C AGAG G C G GAC C AAGAG G C G C C C C AG G C G G G G G C T T C G T G C C AC AGAT G G C AG GAG T G C C AGAG T C C C C T T T T T C TAG GAC C G G AGAG G G C C T G GAT AT C AG G G GAAC A C AG G G C T T T C C A T G G G T G T C C C C A T C T C C T C C AC AG C AG A G G C T G C C A C T G C T G G A G T G C AC C C C T C AGAG C C AG T C C GAG T C T AAGAAGAAT AGAAG G G G C G G C C G C GAG GAC AT C C T G G A GAAG T G G A T C AC C AC A C G C A G AAA AG C T GAAG AAC T G G A A A AG GAC C T GAG GAAG G C C CGCAAAACAAT CAAGAAGC T G GAG GAT GAGAACCC T T GGC T GGGCAAT AT CAT CGGAAT T AT C AG GAAG G G C AAG GAT G G C GAAG G C G C C C C AC C T G C AAAG C G G C C AAG GAC T GAT C AGAT G GAAAT C GAT AG C G GAAC AG G C A A G C G G C C C C AC A A G T C C G G C T T C AC C GAC AAG G G AGAGAG GAT C AC AGAAG G C G C AAG G C C C T G GAGAAC AGAAGAAG C AAT T AAG C AG C G G C G G C AAGAAT C T G T C C AG AGAAGAAG AG GAG GAG C T G G G C AG AC T GAC C G T G GAG GAC GAG G A G C G GAG A A G G C G C G T G G C AG GAC C T C G C AC AG G C G A T G T GAAC C T G T C C G G A G GAG G A C C TAG G G GAG C AC C AG GAG GCGGCTTCGT G C C AC G CAT G GAG G G C G T G C C AGAG T C T C C C T T T A C C C G C AC C G GAG AG G G C C T G GAC A T C AG G G G C AAT C AG G G C T T T C C C T G G G T C C G C C C C T C C C C C C C T C A G C AG AG AC TGCCCCTGCTG GAAT G C AC A C C AC AG

SEQ ID NO: 33 delta 5 codon optimized with restriction sites (Hindlll /EcoRI)

A-UAG C T T G CA C CAT GG C C T C AC G G T C AG AG T C AAAG AAAAAT AG G G G G G G G C G G G AAG AA AT C C T G GAAC AG T G G G T C G GAG C AC G GAAAAAAC T G GAAGAG C T G GAGAG G GAC C T G C G C AAGAT C AG AAGAAGAT C AG AAG C T G GAG GAG GAGAAC C C C T G G C T G G G C AAT AT C AAG GGCATCCTGGGCAAGAAGGATCGGGAGGGAGAGGGAGCACCACCTGCAAAGAGGGCCAGA G C C GAC C AGAT G GAG G T G GAT AG C G G C C C TAG GAAG C G C C CAT T C AGAG G C GAG T T T AC C GACAAGGAGCGGAGAGATCACAGGCGCCGGAAGGCCCTGGAGAACAA.GCGGAAGCAGCT G AGCTCCGGCGGCAAGTCCCTGTCTAAGGAGGAGGAGGAGGAGCTGAGAAAGCTGACAGAG GAG GAC GAG AG AAG G GAG C G C C G G G T G G C C G G C C C AAG G G T G G G C G G C G T GAAC C C C C T G GAG G GAG GAAC C G G G GAG C C C T G GAG GAG G C T T C G T G C CAT C TAT G C AG G G C G T G C C T GAGAG C C CAT T T G C C AG GAC AG GAGAG G G C C T G GzAT GTGCGCGG C AAT C AG GGCTTCCC C T G G GAC AT C C T G T T T C C T G C C GAT C C AC C C T T C AG C C C AC AG T C C T G C AG G C C T C AGAG C AGAT C C G A G T C T AAG A AG A A C AG G G GAG G AAG AG AG GAG G T G C T G GAG C AG T G G G T G AAT GGC C G GAAGAAG C T G GAG GAG C T G GAG C G G GAG C T GAGAAG G G C C AGAAAGAAGAT C AAG AAG C T G GAAG C GA T AAT C C T T G G C T G G G C AAT G T GAAAG G C T C C T G G G C AAG AAG G C AAG GAT G GAGAG G GAG C AC C T C C AG C AAAGAG G G C AAGAAC C GAC C AG AT G G AGAT C GAT AG C G GAC C AAG GAAG C G C C C T C T GAGAG GAG G C T T C AC AGAC C G G GAGAGAC AG GAT C AC C G C C G G G AAAG G C C C T G AAG AAC A GAAGAAG C G C T G T C C G C C G GAG G C AAG G C C T G T C C AAAG AAG AG GAAGAG GAG C T GAAGAG G C T GAC C C G C GAG GAC GAG GAG C G GAAGAAG GAG GAG C AC G G C C C T T C C AGAC T G G G C G T GAAT C CAT C T GAG G GAG GAC C AG G G GAG C A C C AG G C G GCGGCTTCGTGC C AAG CAT G C AG G G C A T C C C C GAG T C C C G G T T T AC C AGAAC A G GAGAG G G C C T G GAC G T GAG GGGCTCTCGCGGCTTTC C T C AG GAC AT CCTGTTCC C AAG C GAT C C C C C T T T T T C T C C AC A GAG C T G T C G C C C C C AG G G A A G C G G G C T C T AAC T T C AG C CTGCTGAAGCAGGCTGGAGACGTGGAGGAGAACCCTGGACCTATGTCTCAGAGCGAGACA AG GAG G G G C C G GAGAG GAAC C AG G GAG GAGAC AC T G GAGAAG T G GAT C AC AG C C AGAAAG AAGGCCGAGGAGCTGGAGAAGGACCTGCGGAAGACCAGAAAGACAATCAAGAAGCTGGAA GAAGAAAAT C CAT G G C T G G GAAAT AT C G T G G G CAT CAT C AG GAAG G G C AAG GAC G G C GAG G GAG C AC C AC C AG C C AAGAG G C C T C G C AC T GAT C AGAT G GAG G T G GAT T C C G G C C C T G G C AAG A G G C C AC AC AAG TCTGGCTT C AC AG AC A A G GAGAG G GAG G A C CAT AG G C G C C G G AAG G C C C T G GAAAAC AAGAAGAAG C AAT T AT C T G C C G G C G G C AAGAT C C T GAG C AAAGAG GAA GAGGAGGAGCTGAGAAGGCTGACCGACGAGGATGAGGAGAGGAAGAGGAGGGTGGCAGGA CCAAGAGTGGGCGACGTGAATCCTAGCAGAGGCGGACCAAGAGGCGCCCCAGGCGGGGGC T T C G T G C C AC AG A G G C A G GAG T G C C AG AG C C C C T T T T T C AG G A C C G GAG AG G G C C T G GAT AT C AG G G GAAC AC AG G G C T T T C CAT GGGT GT CCC CAT C T C C T C C AC AG C AGAG G C T G CCAC T GC T GGAGT GCACCCC T CAGAGCCAGT C CGAGT C TAAGAAGAATAGAAGGGGCGGC C G C GAG GAC A T C C T G GAG AAG T G GAT C AC C AC AC G C AG AAAAG C T G AAGAAC T G GAAAAG GAC C T GAG GAAG G C C C G C AAAAC AAT C AAGAAG C T G GAG GAT G AGAAC C C T T G G C T G G G C AAT A T CAT C G GAAT T A T C AG GAAG G G C AAG GA T G G C GAAG G C G C C C C AC C G C AA G C G G C C AAG GAC T GAT C AGAT G GAAAT C GAT AG C G GAAC AG G C AAG C G G C C C C AC AAG T C C G G C T T C AC C GAC AAG GAG AGAG AG GAT C AC AGAAG G C G C AAG G C C C T G GAGAAC AAGAAGAAG C AAT T AAG C AG C G G C G G C AAG AAT C T G T C C AG AG A A GAAG AG G A G GAG C T G G G C AG AC T G AC C G T G GAG GAC GAG GAG C G GAG AAG GCGCGT GG C AG GAC C T C G C AC AG G C GAT G T G AC C T G T C C G GAG GAG GAC C T AG G G GAG C AC C A G GAG G C G G C T T C G T G C C AC G CAT G GAG G G C G T G C C AGAG T C T CCC T T T AC C C G C AC C G GAGAG G G C C T G GAC AT C AG G G G C AAT C AG G G C T T T C C C T G G G T C C G C C C C T C C C C C C C T C AG C AG AGAC T G C C C C T G C T G GAAT G C AC AC C A CAGTGAT GAGUAAT T CC G T

SEQ ID NO: 34 delta 5 protein

MASRSESKKNRGGREEILEQW\ ^r GAR KLEELERDLRKIKKKIKKLEEENPWLGNI

KGttXiKKDREGEGAPPAKRARADQMEVDSGPRKRPFRGEFTD ERRDi-IR_RRKAL

ENKRKQLSSGGKSLSKEEEEELRKLTEEDERRERRVAGPRVGGVNPLEGGTRGAP

GGGFVPSMQGVPESPFARTGEGLDVRGNQGFPWDILFPADPPFSPQSCRPQSRSES

KKNRGGREE\'XEQW\TSfGRKKLEELERELRRARXKIKKLEDDNPWLGN ¾GIL.G

KKDKDGEGAPPA RARTDQMEIDSGPRKRPLRGGFTDRERQDFtRRRKAL N K

KQLSAGGKSLSKEEEEELKRLTREDEER KEEHGPSRLGVNPSEGGPRGAPGGGF

VPSMQGIPESRFTRTGEGLDVRGSRGFPQDILFPSDPPFSPQSCRPQGSGATNFSLL

KQAGDVEENPGPMSQSETRRGRRGTREETLEKWITARKKAEELEKDLRKTRKTIK

KLEEENPWLGNIVGIIRKGKDGEGAPPAKRPRTDQMEVDSGPGKRPHKSGFTDKE

REDHRRRKALENK KQLSAGGKILSKEEEEELRRLTDEDEERKRRVAGPRVGDV

NPSRGGPRGAPGGGFVPQMAGVPESPFSRTGEGLDIRGTQGFPWVSPSPPQQRLP

LLECTPQSQSESKKNRRGGREDILEKWITTRRKAEELEKDLRKARKTIKKLEDENP

WLGNriGIIRKGKDGEGAPPAKRPRTDQMEIDSGTGKRPH SGFTDKEREDFlRRR

KALENK KQLSSGGKNLSREEEEELGRLTVEDEERRRRVAGPRTGDVNLSGGGP

RGAPGGGFWRMEGVPESPFTRTGEGLDIRGNQGFPWVRPSPPQQRLPLLECTPQ

SEO ID NO: 35 delta 6 wt

AGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCGCGAAGAAATTCTGGAA

C AGTGGGTGGGC GC GC GC A AA AA AC TGGA AGAAC TGGAAC GC GATC TGC GC

AAAATTAAAAAAAAAATTAAAAAACTGGAAGAAGAAAACCCGTGGCTGGGC

AACATTAAAGGCATTCTGGGCAAAAAAGATCGCGAAGGCGAAGGCGCGCCG

CCGGCGAAACGCGCGCGCGCGGATCAGATGGAAGTGGATAGCGGCCCGCGC

AAACGCCCGTTTCGCGGCGAATTTACCGATAAAGAACGCCGCGATCATCGCC

GCCGCAAAGCGCTGGAAAACAAACGCAAACAGCTGAGCAGCGGCGGCAAAA

GCCTGAGCAAAGAAGAAGAAGAAGAACTGCGCAAACTGACCGAAGAAGATG

AACGCCGCGAACGCCGCGTGGCGGGCCCGCGCGTGGGCGGCGTGAACCCGCT

GGAAGGCGGCACCCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAG

GGCGTGCCGGAAAGCCCGTTTGCGCGCACCGGCGAAGGCCTGGATGTGCGCG

GCAACCAGGGCTTTCCGTGGGATATTCTGTTTCCGGCGGATCCGCCGTTTAGC

CCGC AGAGCTGCCGCCCGC AGG GAAG C G GAG C TAG TAAC T T C AGCC T GC T GAAG CAG

G C T G GAG AC G T G GAG GAGAAC C C T G GAC C T ATG AGC C GC AGC G A A AGC A A A A A A A

ACCGCGGCGGCCGCGAAGAAGTGCTGGAACAGTGGGTGAACGGCCGCAAAA

AACTGGAAGAACTGGAACGCGAACTGCGCCGCGCGCGCAAAAAAATTAAAA AACTGGAAGATGATAACCCGTGGCTGGGCAACGTGAAAGGCATTCTGGGCAA

AA AAGAT A A AGATGGC GA AGGC GCGC CGC C GGC GA A ACGC GC GC GC AC C GA

TCAGATGGAAATTGATAGCGGCCCGCGCAAACGCCCGCTGCGCGGCGGCTTT

ACCGATCGCGAACGCCAGGATCATCGCCGCCGCAAAGCGCTGAAAAACAAA

AAAAAACAGCTGAGCGCGGGCGGCAAAAGCCTGAGCAAAGAAGAAGAAGAA

GAACTGAAACGCCTGACCCGCGAAGATGAAGAACGCAAAAAAGAAGAACAT

GGCCCGAGCCGCCTGGGCGTGAACCCGAGCGAAGGCGGCCCGCGCGGCGCG

CCGGGCGGCGGCTTTGTGCCGAGCATGCAGGGCATTCCGGAAAGCCGCTTTA

CCCGCACCGGCGAAGGCCTGGATGTGCGCGGCAGCCGCGGCTTTCCGCAGGA

TATTCTGTTTCCGAGCGATCCGCCGTTTAGCCCGCAGAGCTGCCGCCCGCAGG

G A AG C G GAG C T AC T A AC T T C AG C C G C T G A AG C A G G C T G GAG AC G T G GAG GAG A AC C C T G

GACCTATGAGCCAGAGCGAAACCCGCCGCGGCCGCCGCGGCACCCGCGAAGA

AACCCTGGAAAAATGGATTACCGCGCGCAAAAAAGCGGAAGAACTGGAAAA

AGATCTGCGCAAAACCCGCAAAACCATTAAAAAACTGGAAGAAGAAAACCC

GTGGCTGGGC AACATTGTGGGCATTATTCGCAAAGGCAAAGATGGCGAAGGC

GCGCCGCCGGCGAAACGCCCGCGCACCGATCAGATGGAAGTGGATAGCGGCC

CGGGCAAACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACGCGAAGATCA

TCGCCGCCGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAGCGCGGGCGG

CAAAATTCTGAGC AAAGAAGAAGAAGAAGAACTGCGCCGCCTGACCGATGA

AGATGAAGAACGCAAACGCCGCGTGGCGGGCCCGCGCGTGGGCGATGTGAA

CCCGAGCCGCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGCAG

ATGGCGGGCGTGCCGGAAAGCCCGTTTAGCCGCACCGGCGAAGGCCTGGATA

TTCGCGGCACCCAGGGCTTTCCGTGGGTGAGCCCGAGCCCGCCGCAGCAGCG

CCTGCCGCTGCTGGAATGCACCCCGCAGGGAAGCGGAGCTACTAACT TCAGCCTGC

TGAAGCAGGCTGGAGACGTGGAGGAGAACCCTGGACCTATGAGCCAGAGCGAAAGC

AAAAAAAACCGCCGCGGCGGCCGCGAAGATATTCTGGAAAAATGGATTACCA

CCCGCCGC AAAGCGGAAGAACTGGAAAAAGATCTGCGCAAAGCGCGCAAAA

CCATTAAAAAACTGGAAGATGAAAACCCGTGGCTGGGCAACATTATTGGCAT

TATTCGCAAAGGCAAAGATGGCGAAGGCGCGCCGCCGGCGAAACGCCCGCG

CACCGATCAGATGGAAATTGATAGCGGCACCGGCAAACGCCCGCATAAAAGC

GGCTTTACCGATAAAGAACGCGAAGATCATCGCCGCCGCAAAGCGCTGGAAA

ACAAAAAAAAACAGCTGAGCAGCGGCGGCAAAAACCTGAGCCGCGAAGAAG

AAGAAGAACTGGGCCGCCTGACCGTGGAAGATGAAGAACGCCGCCGCCGCG

TGGCGGGCCCGCGCACCGGCGATGTGAACCTGAGCGGCGGCGGCCCGCGCGG

CGCGCCGGGCGGCGGCTTTGTGCCGCGCATGGAAGGCGTGCCGGAAAGCCCG

TTTACCCGCACCGGCGAAGGCCTGGATATTCGCGGCAACCAGGGCTTTCCGTG

GGTGCGCCCGAGCCCGCCGCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCG

CAG

SEQ ID NO: 36 delta 6 wt with restriction sites (HindEII /EeoRI)

A AGC T T GCACCATGGCCAGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCG

(XJAAGAAATTCTGGAACAGTGGGTGGG(X: GCGCAAAAAACTGGAAGAACT

GGAACGCGATCTGCGCAAAATTAAAAAAAAAATTAAAAAACTGGAAGAAGA

AAACCCGTGGCTGGGCAACATTAAAGGCATTCTGGGCAAAAAAGATCGCGAA

GGCGAAGGCGCGCCGCCGGCGAAACGCGCGCGCGCGGATCAGATGGAAGTG

GATAGCGGCCCGCGCAAACGCCCGTTTCGCGGCGAATTTACCGATAAAGAAC

GCCGCGATCATCGCCGCCGCAAAGCGCTGGAAAACAAACGCAAACAGCTGA

GC AGC GGCGGC A A A AGCC TG AGC A A AG A AGA AG AAGA AG A AC TGC GC A A AC

TGACCGAAGAAGATGAACGCCGCGAACGCCGCGTGGCGGGCCCGCGCGTGG

GCGGCGTGAACCCGCTGGAAGGCGGCACCCGCGGCGCGCCGGGCGGCGGCTT TGTGCCGAGCATGCAGGGCGTGCCGGAAAGCCCGTTTGCGCGCACCGGCGAA GGCCTGGATGTGCGCGGCAACCAGGGCTTTCCGTGGGATATTCTGTTTCCGGC

GGATCCGCCGTTTAGCCCGCAGAGCTGCCGCCCGCAGGGAAGCGGAGCTACTAA

C T T C AG C C T G C T G AAG C AG G C T G GAG AC G T G GAG G AG AAC C C T G GAG C T A TG AGC C GC

AGCGAAAGCAAAAAAAACCGCGGCGGCCGCGAAGAAGTGCTGGAACAGTGG

GTGAAC GGC C GC AA AA AAC TGGAAGA AC TGGA AC GC GA AC TGCGC C GC GCG

CGCAAAAAAATTAAAAAACTGGAAGATGATAACCCGTGGCTGGGCAACGTGA

AAGGCATTCTGGGCAAAAAAGATAAAGATGGCGAAGGCGCGCCGCCGGCGA

AACGCGCGCGCACCGATCAGATGGAAATTGATAGCGGCCCGCGCAAACGCCC

GCTGCGCGGCGGCTTTACCGATCGCGAACGCCAGGATCATCGCCGCCGCAAA

GCGC TG A A A A AC A A A A A A A A AC AGC TG AGC GC GGGC GGC A A A AGC CTG AGC

AAAGAAGAAGAAGAAGAACTGAAACGCCTGACCCGCGAAGATGAAGAACGC

AAAAAAGAAGAACATGGCCCGAGCCGCCTGGGCGTGAACCCGAGCGAAGGC

GGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAGGGCATTC

CGGAAAGCCGCTTTACCCGCACCGGCGAAGGCCTGGATGTGCGCGGCAGCCG

CGGCTTTCCGCAGGATATTCTGTTTCCGAGCGATCCGCCGTTTAGCCCGCAGA

GCTGCCGCCCGC AGG GAAG CGGAGC TAG TAAC T T C AG C C T G C T GAAG CAGG C T GG AGA

CGTGGAGGAGAACCCTGGACCTATGAGCCAGAGCGAAACCCGCCGCGGCCGCCG

CGGCACCCGCGAAGAAACCCTGGAAAAATGGATTACCGCGCGCAAAAAAGC

GGAAGAACTGGAAAAAGATCTGCGCAAAACCCGCAAAACCATTAAAAAACT

GGAAGAAGAAAACCCGTGGCTGGGCAACATTGTGGGCATTATTCGCAAAGGC

AAAGATGGCGAAGGCGCGCCGCCGGCGAAACGCCCGCGCACCGATCAGATG

GAAGTGGATAGCGGCCCGGGCAAACGCCCGCATAAAAGCGGCTTTACCGATA

AAGAACGCGAAGATCATCGCCGCCGCAAAGCGCTGGAAAACAAAAAAAAAC

AGCTGAGCGCGGGCGGCAAAATTCTGAGCAAAGAAGAAGAAGAAGAACTGC

GCCGCCTGACCGATGAAGATGAAGAACGCAAACGCCGCGTGGCGGGCCCGC

GCGTGGGCGATGTGAACCCGAGCCGCGGCGGCCCGCGCGGCGCGCCGGGCG

GCGGCTTTGTGCCGCAGATGGCGGGCGTGCCGGAAAGCCCGTTTAGCCGCAC

CGGCGAAGGCCTGGATATTCGCGGCACCCAGGGCTTTCCGTGGGTG^

AGCCCGCCGCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCGCAGGGAAGCGG

AGC TAC TAAC T T CAGC C T GC T GAAGCAGGC T GGAGACGT GGAGGAGAACCC T GGAC C TA

TG AGC C AG AGC G A A AGC A A A A A A A AC C GC C GC GGC GGC C GC GAAG AT ATT C

TGGAAAAATGGATTACCACCCGCCGCAAAGCGGAAGAACTGGAAAAAGATC

TGCGC AAA GC GCGC AAAACC ATT AAAAAACTGGAAGATGAAAACCCGTGGCT

GGGCAACATTATTGGCATTATTCGCAAAGGCAAAGATGGCGAAGGCGCGCCG

CCGGCGAAACGCCCGCGCACCGATCAGATGGAAATTGATAGCGGCACCGGCA

AACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACGCGAAGATCATCGCCG

CCGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAGCAGCGGCGGCAAAAA

CCTGAGCCGCGAAGAAGAAGAAGAACTGGGCCGCCTGACCGTGGAAGATGA

AGAACGCCGCCGCCGCGTGGCGGGCCCGCGCACCGGCGATGTGAACCTGAGC

GGCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGCGCATGGAAG

GCGTGCCGGAAAGCCCGTTTACCCGCACCGGCGAAGGCCTGGATATTCG^

CAACCAGGGCTTTCCGTGGGTGCGCCCGAGCCCGCCGCAGCAGCGCCTGCCG

CTGCTGGAATGCACCCCGCAGTGAT GAGUAAT T CC GT

SEQ ID NO: 37 delta 6 codon optimized

GCC T CACGGT CAGAGT CAAAGAAGAACAGAGGCGGAAGAGAAGAAAT CC T GGAGCAGT GG G T CGGAGCACGGAAAAAGC T GGAAGAAC T GGAGAGGGACC T GCGCAAGAT CAAGAAGAAG AT C AAG AAG C T GGAGGAGGAGAACCCC T GGC T GGGCAATAT CAAGGGCAT CC T GGGCAAG AAG GA AG G GAG G G AGAG G GAG C AC C AC C T G C AAAGAG G G C C AGAG C C GAC C AG A G GAG G T G GAT AG C G GAC CAAG GAAG C G C C C C T T C C G C G GAGAG T T T AC C GAC AG GAG C G GAGA GAT C AC AG G C G C C G G A AG G C C C G GAG A AC A A GAG G A AG C AG C T GAG C T C C G G C G G CAAG TCCCTGTCTAAGGAGGAGGAGGAGGAGCTGCGCAAGCTGACAGAGGAGGACGAGAGAAGG GAGAG GAG G G T G G C AG GAC C AG G G T G G GAG GAG T GAAT C C T C T G GAG G GAG GAAC C AG A G GAG C AC C AG G A G GAG G C T T C G T G C C A A G CAT G C AG G GAG T G C C AGAG T C C C C C T T T G C C AG GAC AG GAGAG G G C C T G GAC G T GAGAG G C AC C AG GGCT TCCCT TGG GAC AT C C T G T T T C C AG C C GAT C C AC C C T T C AG C C C T C AG T C C T G C AG G C C AC AG G GAAG C G GAG C T AC T AAC T TCAGCCTGCTGAAGCAGGCTGGAGACGTGGAGGAGAACCCTGGACCTATGAGCCGGTCC GAG T C T AGAAGAAT AG G G GAG GAAGAGAG GAG G T G C T G GAG C AG T G G G T GAAC G G C AGA AAGAAGCTGGAGGAGCTGGAGAGGGAGCTGAGAAGGGCCCGCAAGAAGATCAAGAAGC TG GAAG AC GA T AAT C C T T GGC T GGGCAAT GT GAAAGGCAT CC T G G G CAAG AAG GAC A A G GAT G GAGAG G GAG C AC C T C C AG C AAAGAG G G C AAGAAC C GAC C AGAT G GAGAT C GAT AG C G GA C C TAG GAAG C G C C C AC T GAG G G GAG G C T T T AC AG AC C G G GAG AG AC AG G A T C AC C G C C G G AG AAG G C C C T G AG AAC AG AAG AG C AG C T G T C C G C C G GAG G CAAG AG C C T G T C C AAA GAAG AG GAAG AG GAG C T G AG AG G C T GAC C C G C GAG GAC GAG GAGAG G AG AAG GAG GAG CACGGACCATCTAGGCTGGGAGTGAATCCCAGCGAGGGAGGACCAAGGGGAGCACCTGGA G GAG G C T T C G T G C C C T C CAT G C AG G G CAT C C C T GAG TCTCGGT T T AC C AGAAC C GGC GAG G G C C T G G A C G T G G G G G C AG C C G C G G C T T T C C C AG GAC A T C C T G T T C C C C T C C G A T C C C C C T T T T T C T C C C C A GAG C T G T C G C C C T C A A G G A A G C G GAG C T AC T AAC T T C AG C C T G C T G AAG C AG G C T G G AGAC G T G GAG GAGAAC C C T G GAC C TAT G T C T C AGAG C GAG AC AAG GAG G GGCCGGAGAGGAACCAGGGAGGAGACAC TGGAGAAGTGGATCACAGCCCGCAAGAAGGCC GAG GAG C T G GAGAAG GAC C T G C G GAAGAC C AGAAAGAC AT C AG AAG C T G G AG AAG AG AAC C C T T G G C T G G G C AAT AT C G T G G G CAT CAT C AG GAAG G G CAAG GAC G G C GAG G GAG C A CCACCAGCCAAGAGGCCACGCACTGATCAGATGGAGGTGGAT TCTGGACCAGGCAAGCGG C C C C AC AGAG C G G C T T C AC AGAC AG GAGAGAGAG GAC CAT AG G C G C C G GAAG G C C C T G GAAAAGAAGAAGAAGCAAT TAAGCGCCGGCGGCAAGATCCTGTCCAAAGAGGAAGAGGAG GAGCTGAGAAGGCTGACCGACGAGGATGAGGAGAGGAAAAGAAGGGTGGCAGGACCTAGG G T G G G C GAC G T GAAT C CAAG C AG G G GAG GAC C T AGAG GAG C AC C AG GAG G C G G C T T C G T G C C C AG T G G C AG G G T G C C T G G T C C C C T T T T C T C G GAC C G G C G G G G C C T G GAT T C AGAG G C AC AC AG GGCT TCCCCTGGGTGTCCCCT TCT C C T C C AC AG C AG C G G C T G C C T C T G CTGGAGTGCACCCCTCAGGGAAGCGGAGCTACTAACT TCAGCCTGCTGAAGCAGGCTGGA G A C G T G GAG G AG AA C C C T G GAC C T AT G T C G C AG A G C GAAT C T AAG AAG A A TAG AAG G G G C G G C AGAGAG GAT AT C C T G GAGAAG T G GAT C AC C AC AC G C AG AAAAG C T GAAGAAC T GGAA AAG G C C T GAG G AG G C C C G CAAG AC C A T CAAG AAG C T G G G GA T GAAAAT C CAT G G C T G GGAAATATCATCGGCATCATCCGGAAGGGCAAGGACGGGGAAGGCGCCCCACCTGCAAAG C G G C C C AG GAC T GAT C AGAT G GAAAT C GAT T C C G G C AC AG G C AGAG G C C T C AC AG T C T G G C T T C AC GAT AAAG G C G C GAG GAT C C AG AAG G C G CAAG G C C C T G GAG AAC A GAAG AAG C AT TAT C TAG C G G C G G C AAGAAT C T G T C C AGAG AAGAAGAG GAG GAG C T G G G C C G C C T GAC C G T G GAG GAC GAG GAG C G GAGAAG G C G C G T G G C AG GAC C AG AAC AG G C GAT G T G AAC C T G T C T G G A G G C G G C C CAAG GGGCGCCCCC G G C G GAG GCT TCGTGC C A GAAT G G A A G G C G T G C C AGAG TCCCCT T T T AC C C G GAC AG G G GAAG G C C T G GAC AT T AGAG G C AAT C AG G G C T T T C C C T G G G T G C G C C A G C C C C C C T C AG C G C G C T G C C T C T G C T G GAG T G T C C CCTCAG

SEQ ID NO: 38 delta 6 codon optimized with restriction sites (Hindlll /EcoRI)

A-l AG C T T G CA C CAT GG C C T C AC G G T C AG AG T C AAAG AAG AAC AG AG G C G G AG AG AAG AA AT C C T G GAG C AG T G G G T C G GAG C AC G GAAAAAG C T G G AGAAC T G GAGAG G GAC C T G C G C AAGAT CAAGAAGAAGAT C AGAAG C T G GAG GAG GAGAAC C C C T G G C T G G G C AAT AT CAAG G G C A T C C T G G G CAAG AAG G A T AG G GAG G GAGA G G G A G C AC C AC C T G C AAAG A G G G C C AG A G C C GAC C AGAT G GAG G T G GAT AG C G GAC C AG G AG C GCCCCT TCCG C G GAGAG T T T AC C G CAAG GAG C G GAG G AT C AC G G C G C C G GAAG G C C C T G GAG AAC AAG AG GAAG C AG C T G AGCTCCGGCGGCAAGTCCCTGTCTAAGGAGGAGGAGGAGGAGCTGCGCAAGCTGACAGAG G A G G AC GAGA G AAG G GAG AG G A G G G T G G C A G G AC C AAG G G T G G GAG GAG T G ΑΆ C C T C T G GAG G GAG GAAC C AGAG GAG C AC C AG GAG GAG GCT TCGTGC C AAG CAT G C AG G GAG T G C C A GAG T C C C C C T T T G C C A G G AC AG G A GAG G G C C T G G AC G T G A GAG G C AAC C AG G G C T C C C T T G G GAC A CCTGT T TC C AG C C GAT C C AC C C T C AG C C C T C AG C C T G C AG G C C AC AG G GA AG C G GAG C AC T AC T T C AG C C T G C T G AAG C AG G C T G GAGAC G T G GAG GAG AAC C C G G A C C T A T GAG C C G G T C C GAG T C T AAG A AG A AT AG G G G A G G A A GAGA G GAG G T G C T G G A G C AG T G G G T G AC G G C AG AAG AG C T G GAG GAG C T G GAG AG G GAG C T GAG AAG G G C C C G C AAG AAG A C AAGAAG C T G GAAG AC GAT A C C T T G G C T G G G C AAT G T GAAAG G CAT C C T G G G C AAGAAGGACAAGGATGGAGAGGGAGCACCTCCAGCAAAGAGGGCAAGAACCGACCAGATG GAGAT C GAT AG C G GAC C TAG GAAG C G C C C AC T GAG G G GAG G C T T T AC AGAC C G G GAGAGA C A G GAT C AC C G C C G GAG A A AG G C C C T GAAG AC AAG A GAAG C AG C T G T C C G C C G GAG G C AAG A G C C T G T C C A AAG AAG A G G A A GAG GAG C T GAAG AG G C T GAC C C G C GAG GAC G A G GAG AG GAAGAAG GAG GAG C AC G GAC CAT C TAG G C T G G GAG T GMT C C C AG C GAG G GAG GAC C A AGGGGAGCACCTGGAGGAGGCT TCGTGCCC TCCATGCAGGGCATCCCTGAGTCTCGGT T T AC C AGAAC C G G C GAG G G C C T G GAC G T GAG G G G C AG C C G C G G C T T T C C AC AG GAC AT C C T G T T C C C C T C C GAT C C C C C T T T T T C T C C C C AGAG C T G T C G C C C T C AAG GAAG C G GAG C T AC T AAC T T C AG C C T G C T GAAG C AG G C T G GAGAC G T G GAG GAGAAC C C T G GAC C T AT G T C T C AG AG C GAGAC AG GAG G G G C C G GAGAG GAAC C AG G GAG GAGAC AC T G GAGAAG T G GAT C AC A GCCCGCAAGAAGGCCGAGGAGCTGGAGAAGGACCTGCGGAAGACCAGAAAGACAATCAAG AAGC T G GAAG AAGA GAAC C C T T GGC T GGGCAATAT CGT GGGCAT CAT C AG GAAG G G C A AG GAC G G C GAG G GAG C AC C AC C AG C C AAG AG G C C AC G C AC T GAT C AGAT G GAG G T G GAT T C T G GAC C AG G C AAG C G G C C C C A C AAG AG C G G C T T C AC A GAC A AG G A GAGA GAG GAC C A TAG G C G C C G GAAG G C C C T G GAAAAC AAGAAGAAG C AAT T AAG C G C C G G C G G C AAGAT C C T G T C C AAAGAG G AAGAG GAG GAG C T GAGAAG G C T GAC C GAC GAG GAT GAG GAGAG G AAAAGAAG G G T G G C AG GAC C TAG G G T G G G C GAC G T GAAT C C AAG C AG G G GAG GAC C T AGAG GAG C AC C A G GAG GCGGCT TCGTG C C AC AGAT G G C AG GAG T G C C T GAG T C C C CAT T T T C T C G GAC C G G C GAGGGCCTGGATATCAGAGGCACACAGGGC T TCCCCTGGGTGTCCCCT TC TCCTCCACAG C AG CGGCTGCCTCTGCT G G A G T G C AC C C C T C A G G GAAG C G GAG C TACT AAC T T C AG C C T G C T GAAG C AG G C T G GAGAC G T G GAG GAGAAC C C T G GAC C TAT G T C G C AGAG C GAAT C T AAG AAGAA.TAGAAGGGGCGGCAGAGAGGATATCCTGGAGAAGTGGATCACCACACGCAGAAA A G C T GAAGAAC T G GAAAAG GAC C T GAG GAAG G C C C G C AGAC CAT C AAGAAG C T G GAG GAT G AAAAT C CAT G G C T G G G AAAT AT CAT C G G CAT CAT C C G GAAG G G C AAG GAC G G G GAAG G C G C C C C A C C T G C AA G C G G C C C A G GAC T GAT C AG A T G G A AAT C GAT T C C G G C AC A G G C A AG AG G C C T C AC AAG TCTGGCT T C AC AGAT AAAGAG C G C GAG GAT C AC AGAAG G C G C AAG G C C C TGGAGAACAAGAAGAAGCAAT TAT C T A G C G G C G G C A AG A AT C T G T CC AG AG A AG A AG AG G A G GAG C T G G G C C G C C T G AC C G T G G A G GAC GAG GAG C G GAGAAG G C G C G T G G C A G GAC C A AGAAC AG G C GAT G T GAAC C T G T C T G GAG G C G G C C C AAG G G G C G C C C C C G G C G GAG G C T T C G T G C C AAG AT G GAAG G C G T G C C A GAG T C C C C T T T T AC C C G GAC AG G G GAAG G C C T G GAC AT T AGAG G C AAT C AG GGCT T TCCCTGGGTGC GAC C AAG C C C C C C T C AG C AG C GAC T G C C T C T G C T G GAG T G T AC C C C T CAGTGAT GAG AAT T C C G T

SEQ ID NO: 39 delta 6 protein

MASRSESKKNRGGREEIITiQWV

KGILGKKDREGEGAPPAKRARADQMEVDSGPRKRPFRGEFTD ERRDHRRRKAL ENKRKQLSSGGKSLSKEEEEELRKLTEEDERRERRVAGPRVGGVNPLEGGTRGAP GGGFVPSMQGVPESPFARTGEGLDVRGNQGFPWDILFPADPPFSPQSCRPQGSGA TNFSLLKQAGDVEENPGPMSRSESKKNRGGREEVLEQWVNGRKKLEELERELRR ARKKIKKLEDDNPWLGNVKGILGKKDKDGEGAPPAKRARTDQMEIDSGPRKRPL RGGF TDRERQD HRRRK ALKNK KQL S AGGK SL SKEEEEELKRLTREDEERKKEE HGP SRLGVNP SEGGPRGAPGGGF VP SMQGIPESRFTRTGEGLD VRGSRGFPQDILF P SDPPF SPQ SCRPQGSG ATNF SLLKQ AGD VEENPGPM SQ SETRRGRRGTREETLEK WITARKKAEELEKDLRKTR TI KLEEENPWLGNIVGIIRKGKDGEGAPPAKRPRT DQMEVDSGPGKRPHKSGFTD EREDHRRRKALENKKKQLSAGGKILS EEEEEL RRLTDEDEERKRRVAGPRVGDVNPSRGGPRGAPGGGF QMAGVPESPFSRTGE GLDIRGTQGFPWVSPSPPQQRLPLLECTPQGSGATTSiFSLLKQAGDVEENPGPMSQ

SESKKNRRGGREDILFXWITTRRKAEF EKM _^

KGK DGEGAPPAKRPRTDQMEIDSGTGK RPHKSGFTDK EREDHRRRK ALENKKK QLSSGGK LSREEEEELGRLTVEDEERRRRVAGPRTGDVNLSGGGPRGAPGGGF

VPR 4EGVPESPFTRTGEGLDIRGNQGFPW ⁷ RPSPPQQRLPLLECTPQ

SEQ ID NO: 40 delta 7 wt

AGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCGCGAAGAAATTCTGGAA CAGTGGGTGGGCGCGCGCAAAAAACTGGAAGAACTGGAACGCGATCTGCGC

AAAATTAAAAAAAAAATTAAAAAACTGGAAGAAGAAAACCCGTGGCTGGGC

AACATTAAAGGCATTCTGGGCAAAAAAGATCGCGAAGGCGAAGGCGCGCCG

CCGGCGAAACGCGCGCGCGCGGATCAGATGGAAGTGGATAGCGGCCCGCGC

AAACGCCCGTTTCGCGGCGAATTTACCGATAAAGAACGCCGCGATCATCGCC

GCCGCAAAGCGCTGGAAAACAAACGCAAACAGCTGAGCAGCGGCGGCAAAA

GCCTGAGCAAAGAAGAAGAAGAAGAACTGCGCAAACTGACCGAAGAAGATG

AACGCCGCGAACGCCGCGTGGCGGGCCCGCGCGTGGGCGGCGTGAACCCGCT

GGAAGGCGGCACCCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAG

GGCGTGCCGGAAAGCCCGTTTGCGCGCACCGGCGAAGGCCTGGATGTGCGCG

GCAACCAGGGCTTTCCGTGGGATATTCTGTTTCCGGCGGATCCGCCGTTTAGC

CCGCAGAGCTGCCGCCCGCAGAGCCGCAGCGAAAGCAAAAAAAACCGCGGC

GGCCGCGAAGAAGTGCTGGAACAGTGGGTGAACGGCCGCAAAAAACTGGAA

GAACTGGAACGCGAACTGCGCCGCGCGCGCAAAAAAATTAAAAAACTGGAA

GATGATAACCCGTGGCTGGGCAACGTGAAAGGCATTCTGGGCAAAAAAGATA

AAGATGGCGAAGGCGCGCCGCCGGCGAAACGCGCGCGCACCGATCAGATGG

AAATTGATAGCGGCCCGCGCAAACGCCCGCTGCGCGGCGGCTTTACCGATCG

CGAACGCCAGGATCATCGCCGCCGCAAAGCGCTGAAAAACAAAAAAAAACA

GCTGAGCGCGGGCGGCAAAAGCCTGAGCAAAGAAGAAGAAGAAGAACTGAA

ACGCCTGACCCGCGAAGATGAAGAACGCAAAAAAGAAGAACATGGCCCGAG

CCGCCTGGGCGTGAACCCGAGCGAAGGCGGCCCGCGCGGCGCGCCGGGCGG

CGGCTTTGTGCCGAGCATGCAGGGCATTCCGGAAAGCCGCTTTACCCGCACC

GGCGAAGGCCTGGATGTGCGCGGCAGCCGCGGCTTTCCGCAGGATATTCTGT

TTCCGAGCGATCCGCCGTTTAGCCCGCAGAGCTGCCGCCCGCAGGGCACCAA

CCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGG

CGTTTCGCGCGAACAGCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGA

TACCTGGCCGGATGCGAACAAAGTGGGCGGCCAGAACCTGAGCACCAGCAAC

CCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACAC

CGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCG

AACAAAGTGGGC

SEQ ID NO: 41 delta 7 wt with restriction sites (Hindffl /EcoRI)

A AGC T T GCA CCATGGCCAGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCG

CGAAGAAATTCTGGAACAGTGGGTGGGCGCGCGCAAAAAACTGGAAGAACT

GGAACGCGATCTGCGCAAAATTAAAAAAAAAATTAAAAAACTGGAAGAAGA

AAACCCGTGGCTGGGCAACATTAAAGGCATTCTGGGCAAAAAAGATCGCGAA

GGCGAAGGCGCGCCGCCGGCGAAACGCGCGCGCGCGGATCAGATGGAAGTG

GATAGCGGCCCGCGCAAACGCCCGTTTCGCGGCGAATTTACCGATAAAGAAC

GCCGCGATCATCGCCGCCGCAAAGCGCTGGAAAACAAACGCAAACAGCTGA GCAGCGGCGGCAAAAGCCTGAGCAAAGAAGAAGAAGAAGAACTGCGCAAAC

TGACCGAAGAAGATGAACGCCGCGAACGCCGCGTGGCGGGCCCGCGCGTGG

GCGGCGTGAACCCGCTGGAAGGCGGCACCCGCGGCGCGCCGGGCGGCGGCTT

TGTGCCGAGCATGCAGGGCGTGCCGGAAAGCCCGTTTGCGCGCACCGGCGAA

GGCCTGGATGTGCGCGGCAACC AGGGCTTTCCGTGGGATATTCTGTTTCCGGC

GGATCCGCCGTTTAGCCCGCAGAGCTGCCGCCCGCAGAGCCGCAGCGAAAGC

AAAAAAAACCGCGGCGGCCGCGAAGAAGTGCTGGAACAGTGGGTGAACGGC

CGCAAAAAACTGGAAGAACTGGAACGCGAACTGCGCCGCGCGCGCAAAAAA

ATTAAAAAACTGGAAGATGATAACCCGTGGCTGGGCAACGTGAAAGGCATTC

TGGGCAAAAAAGATAAAGATGGCGAAGGCGCGCCGCCGGCGAAACGCGCGC

GCACCGATCAGATGGAAATTGATAGCGGCCCGCGCAAACGCCCGCTGCGCGG

CGGCTTTACCGATCGCGAACGCCAGGATCATCGCCGCCGCAAAGCGCTGAAA

AACAAAAAAAAACAGCTGAGCGCGGGCGGCAAAAGCCTGAGCAAAGAAGAA

GAAGAAGAACTGAAACGCCTGACCCGCGAAGATGAAGAACGCAAAAAAGAA

GAACATGGCCCGAGCCGCCTGGGCGTGAACCCGAGCGAAGGCGGCCCGCGC

GGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAGGGCATTCCGGAAAGCC

GCTTTACCCGCACCGGCGAAGGCCTGGATGTGCGCGGCAGCCGCGGCTTTC^

GCAGGATATTCTGTTTCCGAGCGATCCGCCGTTTAGCCCGCAGAGCTGCCGCC

CGCAGGGCACCAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCAT

CAGCTGGATCCGGCGTTTCGCGCGAACAGCGCGAACCCGGATTGGGATTTTA

ACCCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCGGCCAGAACC

TGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCG

TTTCGCGCGAACACCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATA

CCTGGCCGGATGCGAACAAAGTGGGC TGAT GAG AAT T C CGT

SEQ ID NO: 42 delta 7 codon optimized

G C C T C AC G G T C T GAG T C AAA GAAG AAT C G G G G G G G A AG AG AAG A ΑΆΤ C C T G G AAC A G T G G G T C G G C G C AC G GAAAAAAC T G GAAGAAC G GAG C G G GAC C GAGAAAGAT C AAGAAGAAG AT C AAG AG C T G GAG GAAGAGAAC C C C T G G C T G G G C AA TAT C AAG G G CAT C C G G G C AAG AAG GAT C G G GAG G G C GAG G GAG C AC CAC C T G C AAAG AG G G C AAG G G C AGAC C AGAT G GAG G T G GAT T C C G GAC C AG GAAG C G G C C C T T C C G G G GAG AG T T TAG C GAC AAG GAG C G GAGA GATCACAGGCGCCGGAAGGCCC TGGAGAACAAGCGGAAGCAGCTGAGCTCCGGCGGCAAG T C T C T GAG C AAG GAG GAG GAG GAG GAG C T GAG AAAG C T G AC AG AG G AG GAC GAG AG AAG G GAG C G C C G G G T G G C C G G C C C AAG G G T G G G C G G C G T G AAC C C C C T G GAG G GAG G AAC C AG G G GAG CAC CAG GAG G AG G C T T C G T G C C T T C T AT G C AG G G C G T G C CAG AGAG CCCCT T TGCC AG GAC AG GAGAG G G C C T G GAT G T G C G C G G C AAT C AG G G C T T C C CAT G G GAC AT C C T G T T T C C C G C C G A T C C A C C C T T C T C C C C T CAG T C T T G CAG G C CAC AG T C C C G C T C T GAG AG C AAG A A G. AAC AG G G GAG GAAG G GAG GAG G T G C T G GAG CAG T G G G T G AAT G G CAG GAAG AAG C T G GAG GAG C T G GAG C G G GAG C T GAG AAG G G C C AGAAAGAAG AT C AAGAAG C T G GAAG AC GAT AAT C C T T G G C T G G G C A AT G T G AA G G C A T C C T G G G C A AG A AG G A C AAG GAT G GAGA G G G A G CAC C T C CAG C AAAGAG G G CAC G CAC C GAC C AGAT G GAGAT C GAT T C C G GAC C AAG GAAG C G G C C C C T GAG G G GAG G C T T CAC AGAC AG G GAG C G C CAG GAT CAC C G C C G G AGAAAG G C C C T GAAG A A C. AAG AAG A AG C A G C T G T C T G C C G G C G G C AAG TCCCTGTCT A AAG AAG A G GAG GAG GAG C T GAAG C G G C T GAC CAG AG AG GAC GAG GAG C G GAAG AAG GAG GAG CAC G G C C C T T C CAG A C T G G G C G T G AAT C CAT C T G A G G G A G GAC C AAG G G C G C C C C T G G C G G A G G C T T C G T G C C TAG CAT G CAG G G CAT C C C A GAG T C CAG G T T T AC C A G. AAC C G G A GAG G G C C T G GAC G T G C G G G G C T C T AGAG G C T T T C C C CAG GAC AT C C T G T T C C C TAG C GAT C C C C C T T T TAG C C C C CAG T C C T G TAG G C C T CAG G G CAC C AAC C T G A G CAC AT C C AAT C CAC T G G G C T T C T T T C C AGAC CAC CAG C T G GzAT C CAG CCT TCCGCGC C AAC AG C G C C AAT C C AGAC T G G GAC T T C AAC C C C AA AAG GAC AC C T G G C C T GAT G C C AAC AAG G T C G G C G G C C AGAAC C T G T C T AC A AG C AA CCTCTGGGCT TCT T TCC GA T CAC CAG C T G GA CCTGCCT T TCGGGC C A AC A G C C AAC C C T G AC T G G GAC T T C ΑΆΤ C C T AAC AAAG AC AC T T G G C C C GAT G C T AAT AAG G T C GGC

SEQ ID NO: 43 delta 7 codon optimized with restriction sites (HindHI /EcoRI)

A AGCTTGCAC^TGGCCTCACGGTCTGAGTCAAAGAAGAATCGGGGGGGAAGAGAAGAA ATCC GG AAC AG TGGGTCGGCGCACG G AAAAAAC T G G AAG AAC T G GAG C G G GAC C T GAGA

AAGAT C AAGAAGAAGAT C A AG A AG C T G GAG G AAG AG A A C C C C Τ G G C Τ GGGCAAT AT CAAG GGCATCCTGGGCAAGAAGGATCGGGAGGGCGAGGGAGCACCACCTGCAAAGAGGGCAAGG G C AGAC C AG A G GAG G Τ G GAT T C C G GAC C TAG G AAG C G G C C C T C C G G G GAGAG T TAG C G A CAAG GAG C G GAG AG AT C AC A G G C G C C G G AAG G C C C T G GAG AAC A AG C G G AAG C AG C T G AG C T C C GGC G G CAAG T C T C T GAG CAAG GAG GAG GAG GAG GAG C T GAG AAAG C T GAC AG AG GAG GAC G A GAG A AG G GAG C G C C G G G T G G C C G G C C CAAG G G T G G G C G G C G T G A AC C C C C G GAGGGAGGAACCAGGGGAGCACCAGGAGGAGGCTTCGTGCCTTCTATGCAGGGCGTGCCA GAGAG C C C C T T T G C C AG GAC AG GAGAG G G C C T G GAT G T G C G C G G C AAT C AG G G C T T C C C A T G G GAC AT C C G T T T C C C G C C GAT C C AC C C T C T C C C C C AG T C T T G C AG G C C AC A G T C C C G C T C T GAGAG C AAGAAGAAC AG G G GAG G AAG G GAG GAG G T G C T G GAG C AG T G G G T G AAT G G C AG GAAGAAG C T G GAG GAG C T G GAG C G G GAG C T GAGAAG G G C C AG AAAG AAGAT CAAG AAGC T G GAAGAC GAT AAT C C T T GGC T GGGCAAT GT GAAAGGCAT CC T GGGCAAGAAGGAC AAG GAT G GAGAG G GAG C AC C T C C AG C AAAGAG G G C AC G C AC C GAC C AGAT G GAGAT C GAT TCCGGACCAAGGAAGCGGCCCCTGAGGGGAGGCTTCACAGACAGGGAGCGCCAGGATCAC C G C C G GAG A AAG G C C C T G A A G AAC AAG A AG A A G C AG C T G C T G C C G G C G G CAAG T C C C T G T C AAAGAAGAG GAG GAG GAG C T GAAG C G G C T GAC C AGAGAG GAC GAG GAG C G GAAGAAG G A G GAG C AC G G C C C T T C C AGAC T G G G C G G A AT C CAT C T GAG G GAG GAC C A AG A G G C G C C C C T G G C G GAG GCTTCGTGCC TAG CAT G C AG G G CAT C C C AGAG T C C AG G T T T AC C AGAAC C G GAGAG G G C C T G GAC G T G C G G G G C T C AG AG G C T T T C C C C AG GAC AT C C T G T T C C C TAG C GA TCCCCCTT TAG C C C C C AG T C C T G TAG G C C T C AG G G C AC C AAC C T GAG C AC A T C C AAT C C AC TGGGCTTCTTTC C AGAC C AC C AG C T G GAT C C AG C C T T C C G C G C C AAC AG C G C C AAT C C AG AC G G GAC T T C A AC C C C AAT AAG GAC AC C T G G C C GAT G C C AAC AAG G T C G G C G G C C AGAAC C T G T C T AC AAG C AAT CCTCTGGGCTTCTTTCC GAT C AC C AG C T G GAT C C T G C C T T T C G G G C C AAT AC AG C C AAC C C T GAC T G G GAC T T C AA C C T AAC AAAGAC AC T T G G C C C GAT G C T AAT AAG G T C G G C TGAT GAGILAAT T C C G T

SEQ ID NO: 44 delta 7 protein

MAS SESKKNRGGREEILEQWVGARKKLEELERDLRKIKKKIKKLEEENPWLGNI

KGILGKKDREGEGAPPAKRARADQMEVDSGPRKRPFRGEFTDKERRDHRRR AL

ENKRKQLSSGGKSLSKEEEEELRKLTEEDERRERRVAGPRVGGVNPLEGGTRGAP

GGGFVPSMQGVPESPFARTGEGLDVRGNQGFPWDILFPADPPFSPQSCRPQSRSES

KKNRGGREEVLEQWV^GRKKLEELERELRRARKKIKKLEDDNPWLGNVT GILG

KKDKDGEGAPPA RARTDQMEIDSGPRKRPLRGGFTDRERQDHRRRKALKN

KQLSAGGKSLSKEEEEELKRLTOEDEERKKEEHGPSRLGVNPSEGGPRGAPGGGF

VPSMQGIPESRFTRTGEGLDVRGSRGFPQDILFPSDPPFSPQSCRPQGTNLSTSNPL

GFFPDHQLDPAFRANSANPDWDFNPNKDTWPDANKVGGQNLSTSNPLGFFPDHQ

LDPAFRANTANPDWDFNPNKDTWPDAN VG

SEQ ID NO: 45 delta 8 wt

AGCCAGAGCGAAACCCGCCGCGGCCGCCGCGGCACCCGCGAAGAAACCCTG

GAAAAATGGATTACCGCGCGCAAAAAAGCGGAAGAACTGGAAAAAGATCTG CGCAAAACCCGCAAAACCATTAAAAAACTGGAAGAAGAAAACCCGTGGCTG GGCAACATTGTGGGCATTATTCGCAAAGGCAAAGATGGCGAAGGCGCGCCGC

CGGCGAAACGCCCGCGCACCGATCAGATGGAAGTGGATAGCGGCCCGGGCA AACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACGCGAAGATCATCGCCG CCGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAGCGCGGGCGGCAAAAT

TCTGAGCAAAGAAGAAGAAGAAGAACTGCGCCGCCTGACCGATGAAGATGA

AGAACGCAAACGCCGCGTGGCGGGCCCGCGCGTGGGCGATGTGAACCCGAG

CCGCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGCAGATGGCG

GGCGTGCCGGAAAGCCCGTTTAGCCGCACCGGCGAAGGCCTGGATATTCGCG

GCACCCAGGGCTTTCCGTGGGTGAGCCCGAGCCCGCCGCAGCAGCGCCTGCC

GCTGCTGGAATGCACCCCGCAGAGCCAGAGCGAAAGCAAAAAAAACCGCCG

CGGCGGCCGCGAAGATATTCTGGAAAAATGGATTACCACCCGCCGCAAAGCG

GAAGAACTGGAAAAAGATCTGCGCAAAGCGCGCAAAACCATTAAAAAACTG

GAAGATGAAAACCCGTGGCTGGGCAACATTATTGGCATTATTCGCAAAGGCA

AAGATGGCGAAGGCGCGCCGCCGGCGAAACGCCCGCGCACCGATCAGATGG

AAATTGATAGCGGCACCGGCAAACGCCCGCATAAAAGCGGCTTTACCGATAA

AGAACGCGAAGATCATCGCCGCCGCAAAGCGCTGGAAAACAAAAAAAAACA

GCTGAGCAGCGGCGGCAAAAACCTGAGCCGCGAAGAAGAAGAAGAACTGGG

CCGCCTGACCGTGGAAGATGAAGAACGCCGCCGCCGCGTGGCGGGCCCGCGC

ACCGGCGATGTGAACCTGAGCGGCGGCGGCCCGCGCGGCGCGCCGGGCGGC

GGCTTTGTGCCGCGCATGGAAGGCGTGCCGGAAAGCCCGTTTACCCGCACCG

GCGAAGGCCTGGATATTCGCGGCAACCAGGGCTTTCCGTGGGTGCGCCCGAG

CCCGCCGCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCGCAGGGCACCAAC

CTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGC

GTTTCGCGCGAACAGCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGAT

ACCTGGCCGGATGCGAACAAAGTGGGCGGCCAGAACCTGAGCACCAGCAAC

CCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTTTCGCGCGAACAC

CGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATACCTGGCCGGATGCG

AACAAAGTGGGC

SEQ ID NO: 46 delta 8 wt with restriction sites (Hind!II EcoRI)

A AGC T T GCA CCATGGCCAGCCAGAGCGAAACCCGCCGCGGCCGCCGCGGCACC

CGCGAAGAAACCCTGGAAAAATGGATTACCGCGCGCAAAAAAGCGGAAGAA

CTGGAAAAAGATCTGCGCAAAACCCGCAAAACCATTAAAAAACTGGAAGAA

GAAAACCCGTGGCTGGGCAACATTGTGGGCATTATTCGCAAAGGCAAAGATG

GCGAAGGCGCGCCGCCGGCGAAACGCCCGCGCACCGATCAGATGGAAGTGG

ATAGCGGCCCGGGCAAACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACG

CGAAGATCATCGCCGCCGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAG

CGCGGGCGGCAAAATTCTGAGCAAAGAAGAAGAAGAAGAACTGCGCCGCCT

GACCGATGAAGATGAAGAACGCAAACGCCGCGTGGCGGGCCCGCGCGTGGG

CGATGTGAACCCGAGCCGCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTT

GTGCCGCAGATGGCGGGCGTGCCGGAAAGCCCGTTTAGCCGCACCGGCGAAG

GCCTGGATATTCGCGGCACCCAGGGCTTTCCGTGGGTGAGCCCGAGCCCGCC

GCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCGC AGAGCCAGAGCGAAAGC

AAAAAAAACCGCCGCGGCGGCCGCGAAGATATTCTGGAAAAATGGATTACCA

CCCGCCGCAAAGCGGAAGAACTGGAAAAAGATCTGCGCAAAGCGCGCAAAA

CCATTAAAAAACTGGAAGATGAAAACCCGTGGCTGGGCAACATTATTGGCAT

TATTCGCAAAGGCAAAGATGGCGAAGGCGCGCCGCCGGCGAAACGCCCGCG

CACCGATCAGATGGAAATTGATAGCGGCACCGGCAAACGCCCGCATAAAAGC

GGCTTTACCGATAAAGAACGCGAAGATCATCGCCGCCGCAAAGCGCTGGAAA

ACAAAAAAAAACAGCTGAGCAGCGGCGGCAAAAACCTGAGCCGCGAAGAAG

AAGAAGAACTGGGCCGCCTGACCGTGGAAGATGAAGAACGCCGCCGCCGCG

TGGCGGGCCCGCGCACCGGCGATGTGAACCTGAGCGGCGGCGGCCCGCGCGG

CGCGCCGGGCGGCGGCTTTGTGCCGCGCATGGAAGGCGTGCCGGAAAGCCCG

GGTGCGCCCGAGCCCGCCGCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCG

CAGGGCACCAACCTGAGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCA

GCTGGATCCGGCGTTTCGCGCGAACAGCGCGAACCCGGATTGGGATTTTAAC

CCGAACAAAGATACCTGGCCGGATGCGAACAAAGTGGGCGGCCAGAACCTG

AGCACCAGCAACCCGCTGGGCTTTTTTCCGGATCATCAGCTGGATCCGGCGTT

TCGCGCGAACACCGCGAACCCGGATTGGGATTTTAACCCGAACAAAGATACC

TGGCCGGATGCGAACAAAGTGGGCTGATGAGUAATTCCGT

SEQ ID NO: 47 delta 8 optimized

GCCAGTCAGAGCGAGACCCGCAGAGGACGGAGAGGAACACGAGAAGAGACACTGGAGAAA T G GAT T AC AG C AC G GAAGAAG G C AGAAGAG C T G GAGAAG GAC C T GAG GAAGAC C C G C AAG AGAATCAAGAAGCTGGAGGAGGAGAACCCCTGGCTGGGCAATATCGTGGGCATCATCAGG AAG G G C A G GAT G GAG AG G GAG C C C AC C T G C C AAG G G C C T C G C AC A GAC C AG AT G GAG G T G GAT AG C G GAC C AG G C AAG C G G C C C AC AAG T C C G G C T T C AC C GAC AG GAGAGAGAG G T C AC C G G G AAG G AAG G C C C T G G G AAC AAG AAG A G C AG C T G T C C G C C G G C G G C AAG AT C C T G T C T AAG GAG GAG GAG GAG GAG C T G C G C C G G C T GAC AGAC GAG GAT GAG GAGAG G AAGAG AAG G G T G G C AG GAC C AG G G T G G G C GAC G T GAA C C T T C TAG G G GAG GAC C AG G G GAG C C C AG GAG G AG G C T T C G T G C C T C AG T G G C C G G C G T G C C AG G CTCCCTTTAGC C G GAC AG G C GAG G G C C T G GAT AT C AGAG G C AC C C AG GGCTTTCCTTGGGTGTCTC C AAG C C C AC C AC G C AG C G G C T G C C C G C T G G G G C AC C C C C G C C C AG T C G GAG C AG AAG AACAGGAGGGGAGGAAGAGAGGACAT CC T GGAGAAGT GGAT CACCACAAGAAGGAAG G C C GAG GAG C T G GAGAAG GAC C T G C G G AAG G C C AG AAAG AC CAT C AAGAAG C G GAG GAT GAAAAT CC T T G G C T G G G AA TAT CATCGGAAT TAT T AGAAAAGGC AAG GAC G GAGAG GGA G C AC C T C C AG C AAAG C G G C C AAGAAC AGAC C AGAT G GAGAT C GAT T C T G GAAC C G G C AAG AG G C C C C AC AAGAG T G G C T T C AC C GA AAG GAG C G C GAG GAT C AC C G C C G G AGAAAG G C C C T GGAAAAC AAGAAGAAGCAAT T AG CTCCGGCGG C AAGAAT C T GAG C AGAG AGAAGAG GAG GAG CTGGGCCG C C T GAC AG T G GAG GAC GAG GAGAG G C G C C G GAGAG T G G C AG GAC C T AG AAC C G G C G T G T G AC C T G T C C G G G G C G G C C C AG G G G G C AC C T G G G G C G G C T T C G T G C C AC G CAT G GAG GGCGTGCC GAG TCTCCCTT C AC C G GAC AG GAGAG G G C C T G GAC AT C AG AG G C AAT C AG G GAT T C C CAT G G G T G C G G C C C AG C C C AC C T C AG C AGAG AC T G C C T C T G C G GAG T G T AC C C C C AG G G C AC AAAC C T G T C C AC C T C T AAT C C T C T G G G C T T C T T T CCAGACCACCAGCTGGATCCAGCCTTCAGGGCCAACTCCGCCAACCCTGACTGGGACTTC AAC C C T A AAG GAC AC AT G G C C AG AT G C C AC AAG G T C G G C G G C C AGAAC C T GAG C AC C T C C AAT CCCCTGGGCTTCTTTCC GAC C AC C AG C T G G CCCGCCTTTCGCGC C AAT AC C G C C AAT C C C GAC T G G GAC T T C AAT C C AAAT AAG GAC AC C T G G C C C GAT G C T AAC AAAG T G GGA

SEQ ID NO: 48 delta 8 codon optimized with restriction sites (Hindlll /EcoRI)

A AGCTTGCACCATGGCCAGTCAGAGCGAGACCCGCAGAGGACGGAGAGGAACACGAGAA GAGACAC T GGAGAAAT GGAT TAG AGC ACGGAAGAAGGC AGAAG AGC T G G G AG GAC C T G AG G AGAC C C G C AGAC AAT C AAGAAG C T G GAG GAG GAG AAC CCCTGGCTGGG C AAT AT C G T G G G CAT CAT C AG GAAG G G C AAG GAT G GAGAG G GAG C AC C AC C T G C C AGAG G C C T C G C AC AG AC C AG A T G G A G G T G GAT A G C G GAC C A G G C A AG C G G C C T C AC A AG T C C G G C T T C A C C GAC AAG GAGAGAGAG GAT C AC C G GAGAAG GAAG G C C C T G GAGAAC AAGAAGAAG C AG C T G T C C G C C G G C G G C AAG T C C T G T C T AAG G G G G GAG GAG G G C T G C G C C G G C T GAC GAC G A G GAT GAG GAGAG GAAG AG A A G G G T G G C A G GAC C AAG G G T G G G C G AC G T GAAT C C T T C T AG G G GAG GAC C AAG G G GAG C AC C AG GAG GAG G C T T C G T G C C T C AGAT G G C C G G C G T G C C A GAG T C T C C C T T T AG C C G GAC G G C GAG G G C C T G GAT T C GAG G C AC C C AG G G C T T C C T TGGGTGTCTC C AAG C C C AC C AC AG C AG C G G C T G C C AC T G C T G GAG T G C AC AC C C C AG T C C C AG T C T GAGAG C AAG AAGAAC AG GAG G G GAG GAAG AGAG GAC AT C C T G GAGAAG T G GAT C AC C A C AAG AAG GAAG G C C G A G GAG C T G GAG A A G GAC C T G C G G A A G G C C AG A A AG AC CAT C AAGAAGC T GGAGGAT GAAAAT CCT TGGC Τ GGGAAA AT CAT CGGAAT TAT TAGAAAAGGC AAG GAC G GAGAG G GAG C AC C T C C AG C AAG C G G C C AAGAAC AGAC C AGAT G GAGAT C GAT TCTGGAACCGGCAAGAGGCCCCACAAGAGTGGCT TCACCGATAAGGAGCGCGAGGATCAC C G C C G G AGAAAG G C C C T G GAAAAC AAGAAG AAG C AAT T AAG CTCCGGCGG C AAG AAT C T G AG C AG AG AAG AAG AG GAG GAG C T G G G C C G C C T GAC AG T G GAG GAC GAG GAGAG G C G C C G G AGAGTGGCAGGACCTAGAACCGGCGATGTGAACCTGTCCGGAGGCGGCCCAAGGGGAGCA C C T G GAG G C G G C T T C G T G C C AC G CAT G GAG G G C G T G C C T GAG T C T C C C T T C AC C AG GAC A G GAGAG G G C C T G GAC AT C AGAG G C AA C AG G GAT T C C CAT G G G T G C G G C C C AG C C C AC C T C AG C AGAG AC GCCTCTGCTG GAG T G T AC C C C AC AG G G C AC AAAC C T G T C C AC C T C T AAT C C T C T G G G C T T C T T T C C AGAC C AC C AG C T G GAT C C AG C C T T C AG G G C C AAC T C C G C C AAC C C T GAC T G G GAC T C AAC C C AAT AAG GAC AC AT G G C C AGAT G C C AAC AAG G C G G C G G C C AGAAC C T GAG C AC C T C C AA TCCCCTGGGCT TCT T TCCT GAC C AC C AG C T G GAT C C C G C C T T T C G C G C C AAT AC C G C C AA C C C GAC T G G GAC T T C AA C C AAA AAG GAC AC C T G G C C C GAT G C T AAC AAAG T G G GATGAT GAGUAAT T C C G T

SEQ ID NO: 49 delta 8 protein

MASQSETRRGRRGTREETLEKWITARKKAEELEKDLRKTRKTIKKLEEENPWLG

NIVGIIRKGKDGEGAPPA RPRTDQMEVDSGPGKRPHKSGFTDKEREDI-tRRRKAL

ENK KQLSAGGK1LSKEEEEELRRLTDEDEERKRRVAGPRVGDVNPSRGGPRGAP

GGGF VPQMAGVPESPF SRTGEGLDIRGTQGFP W VSPSPPQQRLPLLECTPQ SQ SES

KKNRRGGREDILEKWITTRR AEELEKDLRKARKTIKKLEDENPWLGNIIGIIRKG

KDGEGAPPA RPRTDQMEIDSGTGKRPH SGFTDKEREDHRRRKALENKKKQLS

SGGKNLSREEEEELGRLTVEDEERRRRVAGPRTGDVNLSGGGPRGAPGGGFVPR

MEG ESPFTRTGEGLDIRGNQGFPWVRPSPPQQRLPLLECTPQGTNLSTSNPLGF

FPDHQLDPAFRANSANPDWDFNPNKDTWPDANKVGGQNLSTSNPLGFFPDHQLD

PAFRANTANPDWDFNP KDTWPDANKVG

SEQ ID NO: 50 delta 9 wt

AGC C GC AGC G A A AGC A A A A A A A AC C GC GGC GGC C GC G A AG A A ATT C T GG A A

CAGTGGGTGGGCGCGCGCAAAAAACTGGAAGAACTGGAACGCGATCTGCGC

AAAATTAAAAAAAAAATTAAAAAACTGGAAGAAGAAAACCCGTGGCTGGGC

AACATTAAAGGCATTCTGGGCAAAAAAGATCGCGAAGGCGAAGGCGCGCCG

CCGGCGAAACGCGCGCGCGCGGATCAGATGGAAGTGGATAGCGGCCCGCGC

AAACGCCCGTTTCGCGGCGAATTTACCGATAAAGAACGCCGCGATCATCGCC

GCCGCAAAGCGCTGGAAAACAAACGCAAACAGCTGAGCAGCGGCGGCAAAA

GCCTGAGCAAAGAAGAAGAAGAAGAACTGCGCAAACTGACCGAAGAAGATG

AACGCCGCGAACGCCGCGTGGCGGGCCCGCGCGTGGGCGGCGTGAACCCGCT

GGAAGGCGGCACCCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAG

GGCGTGCCGGAAAGCCCGTTTGCGCGCACCGGCGAAGGCCTGGATGTGCGCG

GCAACCAGGGCTTTCCGTGGGATATTCTGTTTCCGGCGGATCCGCCGTTTAGC

CCGCAGAGC TGC C GC C C GC AG AGC C GC AGC G A A AGC A A A A A A A AC C GC GGC

GGCCGCGAAGAAGTGCTGGAACAGTGGGTGAACGGCCGCAAAAAACTGGAA

GAACTGGAACGCGAACTGCGCCGCGCGCGCAAAAAAATTAAAAAACTGGAA

GATGATAACCCGTGGCTGGGCAACGTGAAAGGCATTCTGGGCAAAAAAGATA

AAGATGGCGAAGGCGCGCCGCCGGCGAAACGCGCGCGCACCGATCAGATGG

AAATTGATAGCGGCCCGCGCAAACGCCCGCTGCGCGGCGGCTTTACCGATCG

CGAACGCCAGGATCATCGCCGCCGCAAAGCGCTGAAAAACAAAAAAAAACA

GCTGAGCGCGGGCGGCAAAAGCCTGAGCAAAGAAGAAGAAGAAGAACTGAA

ACGCCTGACCCGCGAAGATGAAGAACGCAAAAAAGAAGAACATGGCCCGAG

CCGCCTGGGCGTGAACCCGAGCGAAGGCGGCCCGCGCGGCGCGCCGGGCGG CGGCTTTGTGCCGAGCATGCAGGGCATTCCGGAAAGCCGCTTTACCCGCACC GGCGAAGGCCTGGATGTGCGCGGCAGCCGCGGCTTTCCGCAGGATATTCTGT

TTCCGAGCGATCCGCCGTTTAGCCCGCAGAGCTGCCGCCCGCAG

SEQ ID NO: 51 delta 9 wt with restriction sites (Himini /EeoRI)

A AGC T T GCACCATGGCCAGCCGCAGCGAAAGCAAAAAAAACCGCGGCGGCCG

CGAAGAAATTCTGGAACAGTGGGTGGGCGCGCGCAAAAAACTGGAAGAACT

GGAACGCGATCTGCGCAAAATTAAAAAAAAAATTAAAAAACTGGAAGAAGA

AAACCCGTGGCTGGGCAACATTAAAGGCATTCTGGGCAAAAAAGATCGCGAA

GGCGAAGGCGCGCCGCCGGCGAAACGCGCGCGCGCGGATCAGATGGAAGTG

GATAGCGGCCCGCGCAAACGCCCGTTTCGCGGCGAATTTACCGATAAAGAAC

GCCGCGATCATCGCCGCCGCAAAGCGCTGGAAAACAAACGCAAACAGCTGA

GC AGC GGCGGC A A A AGCC TG AGC A A AG AAGAAG AAGAAG A AC TGC GC A A AC

TGACCGAAGAAGATGAACGCCGCGAACGCCGCGTGGCGGGCCCGCGCGTGG

GCGGCGTGAACCCGCTGGAAGGCGGCACCCGCGGCGCGCCGGGCGGCGGCTT

TGTGCCGAGCATGCAGGGCGTGCCGGAAAGCCCGTTTGCGCGCACCGGCGAA

GGCCTGGATGTGCGCGGCAACCAGGGCTTTCCGTGGGATATTCTGTTTCCGGC

GGATCCGCCGTTTAGCCCGCAGAGCTGCCGCCCGCAGAGCCGCAGCGAAAGC

AAAAAAAACCGCGGCGGCCGCGAAGAAGTGCTGGAACAGTGGGTGAACGGC

CGCAAAAAACTGGAAGAACTGGAACGCGAACTGCGCCGCGCGCGCAAAAAA

ATTAAAAAACTGGAAGATGATAACCCGTGGCTGGGCAACGTGAAAGGCATTC

TGGGCAAAAAAGATAAAGATGGCGAAGGCGCGCCGCCGGCGAAACGCGCGC

GCACCGATCAGATGGAAATTGATAGCGGCCCGCGCAAACGCCCGCTGCGCGG

CGGCTTTACCGATCGCGAACGCCAGGATCATCGCCGCCGCAAAGCGCTGAAA

AACAAAAAAAAACAGCTGAGCGCGGGCGGCAAAAGCCTGAGCAAAGAAGAA

GAAGAAGAACTGAAACGCCTGACCCGCGAAGATGAAGAACGCAAAAAAGAA

GAACATGGCCCGAGCCGCCTGGGCGTGAACCCGAGCGAAGGCGGCCCGCGC

GGCGCGCCGGGCGGCGGCTTTGTGCCGAGCATGCAGGGCATTCCGGAAAGCC

GCTTTACCCGCACCGGCGAAGGCCTGGATGTGCGCGGCAGCCGCGGCTTTCC

GCAGGATATTCTGTTTCCGAGCGATCCGCCGTTTAGCCCGCAGAGCTGCCGCC

CGC AGTGAT GAGJJAAT TC C G T

SEQ ID NO: 52 delta 9 codon optimized

G C C AG T C G G A G C G A AT C A A AG A A AA TAG A G G G G G AAG AG A A G AAA T C C T G GAG C AG T G G G T C G G G G C AC G G AAAAAAC T G G A A GAAC T G G A G C G G GAG C T G AG AAAG AT C AAG AA GAAG AT C AAGAAG C T G GAG GAAGAG AAC C C C T G G C T G G G C AAT AT C AAG G G CAT C C T G G G C AAG A A G GAT AG G GAG G G C GAG G GAG C AC C AC C T G C A A AG AG G G C A AG G G C AG A C C AG AT G G G G T G Gx T T C C G GAC C AAG GAAG C G G C C C T T C C G G G GAGAG T T T AC C GAC AAG GAG C G GAGA GAT C AC AG G C G C C G GAAG G C C C G G AGAAC AAG C G GAAG C AG C T GAG C T C C G G C G G C AAG T C T C T GAG C A AG G A G GAG GAG GAG G A G C T GAGAAAGC T GACAGAGGAGGACGAGAGAAGG GAGAG GAG G G T G G C AG GAC C TAG G G T G G GAG G C G T GAAC C C AC T G GAG G GAG GAAC C AG G G GAG C AC C T G GAG GAG G C T T G G C CAT C TAT G C AG G GAG T G C C AGAG AG C C C T T T C G C C AG GAC AG GAGAG G G C C T G GAT G T G C G C G G C AA C AG GGCTTCCCCTGG GAC AT C C T G T T T C C T G C C GAT C C AC C C T T C AG C C C AC AG T C C T G C AG G C C AC AG T C C C G C T C T GAGAG C AAG AAGAACAGGGGAGGAAGGGAGGAGGTGCTGGAGCAGTGGGTGAATGGCCGGAAGAAGCTG GAG GAG C T G GAG C G G GAG C T GAGAAG G G C C AGAAAGAAGAT C AAGAAG C T GGAAGACGAT AA C C T T G G C T G G G C AAT G T GAAAG G CAT C C T G G G C AAG AAG GAC AAG GAT G GAGAG G G A G C AC C T C C AG C AAAGAG G G C AC G C AC C GAC C AGAT G GAGA T C GA T T C T G GAC C TAG GAAG C G G C C C C T GAGAG GAG G C T T T AC AGAC AG G GAG C G C C AG GAT C AC C G C C G GAGAAAG G C C C T GAAG AAC AAG AA GAAG C AG C T GAG C G C C G G C G G C AA G T C C C T G T C T AAAG AA GAG GAG G A G GAG C G A AG C G G C T GAG C A GAGA G G AC GAG GAG C G GAAG AAG GAG G A G C AC G G AC C A T C C AGAC T G G GAG T GAAT C C T T C T GAG G GAG GAC C AAGAG G C G C C C C AG G CGGCGGCT T T G T G C CAAG CAT G C AG G G CAT C C C C GAG T C C AG G T T C AC C AG AAC C G G C G AAG G C C T G GAT G T G C G G G G C A G C AG G G C T T C C C C C A G GAT AT T C T G T T T C C C T C C G AC C C C C C C T T C A G T CCCCAGTCT TGCCGACCTCAG

SEQ ID NO: 53 delta 9 codon optimized with restriction sites (HindlH /EcoRI)

A AGCT T G ¾C(¾TGGCCAGTCGGAGCGAATCAA¾GAA¾AATAGAGGGGGAAGAGAAGAA AT C C T G GAG CAGTGGGTCGGGGCACG G AAAAAAC T G G AAG AAC T G GAG C G G GAC C T GAGA AAGAT CAAGAAGAAGAT CAAGAAGC T GGAGGAAGAGAACCCC T GGC T GGGCAAT AT CAAG G G CAT C C T G G G C AGAAG GAT AG G GAG G G C GAG G GAG C AC C AC C T G C AAA GAG G G CAAG G G C AG AC C AG AT G GAG G T G GA T T C C G GAC CAAG G AAG C G G C C C T T C C G G G GAG AG T T T AC C G A CAAG GAG C G GAG AG AT C AC A G G C G C C G G AAG G C C C T G GAG AAC A AG C G GAAG C AG C T G AG C T C C G G C G G C AG T C T C T GAG C AG GAG GAG GAG GAG GAG C T G AG AAAG C T GAC AG AG GAG GAC G A GAG A AG G GAG AG GAG G G T G G C AG GAC C T AG G G T G G GAG G C G T G A AC C C AC T G GAG G GAG GAAC C AG G G GAG C AC C T G GAG GAG GCT T TGTG C CAT C T AT G C AG G GAG T G C C A GAG AG C C C T T T C G C C AG GAC AG G AGAG G G C C T G GAT G T G C G C G G C AAT C AG G G C T T C C C C T G G GAC AT CCTGT T TCCTGCC GAT C C AC C C T T C AG C C C AC AG T C C T G C AG G C C AC AG C C C G C T C T GAGAG C AAGAAGAAC AG G G GAG GAAG G GAG GAG G T G C T G GAG C AG T G G G T GAAT G G C C G G A AG A AG C T G GAG GAG C T G G A G C G G GAG C T GAG A AG G G C C A G AAA G AAG AT C AAGAAG C T G GAAGAC GAT AAT C C T T GGC T GGGCAAT GT GAAAGGCAT CC T GGGCAAGAAGGAC AAG GAT G GAGAG G GAG C AC C T C C AG C AAAGAG G G C AC G C AC C GAC C AGAT G GAGAT C GAT TC TGGACCTAGGAAGCGGCCCC TGAGAGGAGGCT T TACAGACAGGGAGCGCCAGGATCAC C G C C G GAG AAG G C C C T G AG AAC AG AAG AG C AG C T GAG C G C C G G C G G CAAG T C C C T G T C AAGAAGAG GAG GAG GAG C T GAAG C G G C T GAC C AGAGAG GAC GAG GAG C G GAAG AAG GAG GAG C AC G GAC CAT C C AGAC T G G GAG T GAAT C C T T C T GAG G GAG GAC C AAGAG G C G C C C C AG GCGGCGGCT T TGTG C CAAG CAT G C AG G G CAT C C C C GAG T C C AG G T T C AC C AGAAC C G G C GAAG G C C T G GAT G T G C G G G G C AG C A GAG G C T T C C C C C AG G A TAT T C T G T T T C C C T C C GACCCCCCCT TCAGTCCCCAGTCT TGCCGACCTCAGTGATGAGUAAT TCCGT

SEQ ID NO: 54 delta 9 protein

MASRSESKKNRGGREElLEQWVGARKKLEELERDLi KI K IK LEEENPWLGNI KGILGKKDREGEGAPPAKRARADQMEVDSGPRKRPFRGEFTDi ERRDHRRRKAL ENKRXQLSSGGKSLSKEEEEELRKLTEEDERRERRVAGPRVGGVNPLEGGTRGAP GGGFVPSMQGVPESPFARTGEGLDVRGNQGFPWDILFPADPPFSPQSCRPQSRSES

KKNRGGREEVLEQWVNGR KL^

KKDKDGEGAPPAKRARTDQMEIDSGPRKRPLRGGFTDRERQDHRRRKALKNKK KQLSAGGKSLSKEEEEELKRLTREDEERKKEEHGPSRLGVNPSEGGPRGAPGGGF VP SMQGIPES RFTRTGEGLD VRGSRGFPQD ELF P S DPPF SPQ SC RPQ

SEQ ID NO: 55 delta 10 wt

AGCCAGAGCGAAACCCGCCGCGGCCGCCGCGGCACCCGCGAAGAAACCCTG

GAAAAATGGATTACCGCGCGCAAAAAAGCGGAAGAACTGGAAAAAGATCTG

CGCAAAACCCGCAAAACCATTAAAAAACTGGAAGAAGAAAACCCGTGGCTG

GGCAACATTGTGGGCATTATTCGCAAAGGCAAAGATGGCGAAGGCGCGCCGC

CGGCGAAACGCCCGCGCACCGATCAGATGGAAGTGGATAGCGGCCCGGGCA

AACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACGCGAAGATCATCGCCG

CCGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAGCGCGGGCGGCAAAAT

TCTGAGCAAAGAAGAAGAAGAAGAACTGCGCCGCCTGACCGATGAAGATGA

AGAACGCAAACGCCGCGTGGCGGGCCCGCGCGTGGGCGATGTGAACCCGAG

CCGCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTTGTGCCGCAGATGGCG GGCGTGCCGGAAAGCCCGTTTAGCCGCACCGGCGAAGGCCTGGATATTCGCG

GCACCCAGGGCTTTCCGTGGGTGAGCCCGAGCCCGCCGCAGCAGCGCCTGCC

GCTGCTGGAATGCACCCCGCAGAGCCAGAGCGAAAGCAAAAAAAACCGCCG

CGGCGGCCGCGAAGATATTCTGGAAAAATGGATTACCACCCGCCGCAAAGCG

GAAGAACTGGAAAAAGATCTGCGCAAAGCGCGCAAAACCATTAAAAAACTG

GAAGATGAAAACCCGTGGCTGGGCAACATTATTGGCATTATTCGCAAAGGCA

AAGATGGCGAAGGCGCGCCGCCGGCGAAACGCCCGCGCACCGATCAGATGG

AAATTGATAGCGGCACCGGCAAACGCCCGCATAAAAGCGGCTTTACCGATAA

AGAACGCGAAGATCATCGCCGCCGCAAAGCGCTGGAAAACAAAAAAAAACA

GCTGAGCAGCGGCGGCAAAAACCTGAGCCGCGAAGAAGAAGAAGAACTGGG

CCGCCTGACCGTGGAAGATGAAGAACGCCGCCGCCGCGTGGCGGGCCCGCGC

ACCGGCGATGTGAACCTGAGCGGCGGCGGCCCGCGCGGCGCGCCGGGCGGC

GGCTTTGTGCCGCGCATGGAAGGCGTGCCGGAAAGCCCGTTTACCCGCACCG

GCGAAGGCCTGGATATTCGCGGCAACCAGGGCTTTCCGTGGGTGCGCCCGAG

CCCGCCGCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCGCAG

SEQ ID NO: 56 delta 10 wt with restriction sites (Hindlll /EcoRI)

A AGCT T GCACCATGGCCAGCCAGAGCGAAACCCGCCGCGGCCGCCGCGGCACC

CGCGAAGAAACCCTGGAAAAATGGATTACCGCGCGCAAAAAAGCGGAAGAA

CTGGAAAAAGATCTGCGCAAAACCCGCAAAACCATTAAAAAACTGGAAGAA

GAAAACCCGTGGCTGGGCAACATTGTGGGCATTATTCGCAAAGGCAAAGATG

GCGAAGGCGCGCCGCCGGCGAAACGCCCGCGCACCGATCAGATGGAAGTGG

ATAGCGGCCCGGGCAAACGCCCGCATAAAAGCGGCTTTACCGATAAAGAACG

CGAAGATCATCGCCGCCGCAAAGCGCTGGAAAACAAAAAAAAACAGCTGAG

C GC GGGCGGC AA AATTCTGAGC AA AGAAGA AGAAGA AGAAC TGC GC C GC C T

GACCGATGAAGATGAAGAACGCAAACGCCGCGTGGCGGGCCCGCGCGTGGG

CGATGTGAACCCGAGCCGCGGCGGCCCGCGCGGCGCGCCGGGCGGCGGCTTT

GTGCCGCAGATGGCGGGCGTGCCGGAAAGCCCGTTTAGCCGCACCGGCGAAG

GCCTGGATATTCGCGGCACCCAGGGCTTTCCGTGGGTGAGCCCGAGCCCGCC

GCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCGCAGAGCCAGAGCGAAAGC

AAAAAAAACCGCCGCGGCGGCCGCGAAGATATTCTGGAAAAATGGATTACCA

CCCGCCGCAAAGCGGAAGAACTGGAAAAAGATCTGCGCAAAGCGCGCAAAA

CCATTAAAAAACTGGAAGATGAAAACCCGTGGCTGGGCAACATTATTGGCAT

TATTCGCAAAGGCAAAGATGGCGAAGGCGCGCCGCCGGCGAAACGCCCGCG

CACCGATCAGATGGAAATTGATAGCGGCACCGGCAAACGCCCGCATAAAAGC

GGCTTTACCGATAAAGAACGCGAAGATCATCGCCGCCGCAAAGCGCTGGAAA

ACAAAAAAAAACAGCTGAGCAGCGGCGGCAAAAACCTGAGCCGCGAAGAAG

AAGAAGAACTGGGCCGCCTGACCGTGGAAGATGAAGAACGCCGCCGCCGCG

TGGCGGGCCCGCGC ACCGGCGATGTGAACCTGAGCGGCGGCGGCCCGCGCGG

CGCGCCGGGCGGCGGCTTTGTGCCGCGCATGGAAGGCGTGCCGGAAAGCCCG

TTTACCCGCACCGGCGAAGGCCTGGATATTCGCGGCAACCAGGGCTTTCCGTG

GGTGCGCCCGAGCCCGCCGCAGCAGCGCCTGCCGCTGCTGGAATGCACCCCG

CAGTGAT G AG AAT T C C G T

SEQ ID NO: 57 delta 10 codon optimized

G C C T C A C AG A G C G A AAC A C G G C G G G G G C G GAG G G G AAC TAG A GAG G A AAC AC G G AA A AA T G GAT T AC AG C AC G G AAAAAG G C AGAG GAAC T G GAGAAG GAC C T GAG GAAG AC C C G C AAG AC ΑΔ T C AAG AAG C T G G G GAG GAG AAC C CAT G G C T G G G C AAT AT C G T G G G C A T CAT C C G G

-12 AAG G G C AAG GAT G G AGAG G GAG C AC C AC C T G C AAAGAG G C C C C G C AC C GAC C AG A G GAG G T G Gx T TCTGGCCCTGG C AAGAG G C C AC AC AAGAG C G G C T T C AC AGAC AAG GAG C G C GAG GAT C AC C G GAG A AG G A AG G C C C G GAG A AC A A G AAG AAG C AG C T GAG C G C C G G C G G C AAG ATCCTGTC C A AG G A G GAG GAG GAG G A G C T G C G C C G G C T GAC C GAC GAG G A T GAG GAG C G G AAG AGAAG G G T G G C AG GAC C AAG AG T G G G C GAC G T GAA C C C T C AG G G GAG GAC C AAG G G GAG C AC C T G G A G GAG G C T T C G T G C C T C AG AT G G C A G GAG T G C C AGAG T C C C C T T T T T C T AG GAC C G GAGAG G G C C T G GAT AT C AG G G GAAC AC AG G G C T T T C CAT GGGTGTCTC C AAG C C C AC C AC AG C AG AG G C T G C C AC T G C T G GAG T G C AC C C C T C AG T C C C AG T C T GAG AG C AAG AAGAAC AG GAG G G GAG GAAG G GAG GAC A T C C T G GAG AAG T G GAT C AC C AC AAGAAG GAAG G C C GAG GAG C T G GAG AAG GAC C T G C G G AAG G C C AGAAAAAC AAT C AAGAAG C T G GAAGAT GAGAACCCCTGGCTGGGCAATATCATCGGCATCATCAGAAAAGGCAAGGACGGCGAGGGA G C AC C T C C AG C AAAG C G G C C AGAAC C GAC C AGAT G GAGA T C GA T T C C G G C AC AG G C AAG C G G C C AC AC AAG T C T G G C T T C AC C GAC AAG GAG AGAG AG GAT C AC C G C C G GAG AAAG G C C C T G GAAAAC AAGAAG AAG C AAT T AAG CTCCGGCGG C AAG AAT C T GAG C AG AGAAG AAG AG- GAG GAG C T G G G C AG AC T GAC C G T G GAG GAC G G GAGAG G C G C C G GAG G T G G C AG GAC C C AGAAC AG G C GAT G T GAAC C T GAG C G GAG GAG GAC C TAG G G GAG C AC C AG GAG G C G G C T T C G T G C C T AG A A T G G A G G G C G T G C C AG A G T C C C C C T T T AC C AG GAC AG GAGA G G G C C T G GAC AT C AG G G G C AAT C AG GGCTTTCCCTGGGT C C G C C C T T C AC C AC C AC AG C AGAGAC T G C C C C T GC T GGAAT GC ACAC CACAG

SEQ ID NO: 58 delta 10 codon optimized with restriction sites (HindlE /EcoRI)

A AGCTTGCACCATGGCCTCACAGAGCGAAACACGGCGGGGGCGGAGGGGAACTAGAGAG GAAACACTGGAAAAATGGATTACAGCACGGAAAAAGGCAGAGGAACTGGAGAAGGACCTG AGGAAGACCCGCAAGACAATCAAGAAGCTGGAGGAGGAGAACCCATGGCTGGGCAATATC G T G G G CAT CAT C C G GAAG G G C AAG GAT G GAGAG G GAG C AC C AC C T G C AAAGAG G C C C C G C AC C GAC C AG A T G G A G G T G GAT TCTGGCCCTGG C A AG AG G C C A C AC AAG AG C G G C T T C A C A GAC AAG GAG C G C GAG GXAT C AC C G GAGAAG GAAG G C C C T G GAGAAC AAGAAGAAG C AG C T G AG C G C C G G C G G C A AG A T C C T G T C C AAG GAG G A G GAG GAG GAG C T G C G C C G G C T GAC C GAC G G GAT GAG GAG C G GAAG AG A A G G G T G G C A G GAC C AAG AG T G G G C G AC G T GAAT C C C T C T AG G G GAG GAC C AAG G G GAG C AC C T G GAG GAG G C T T C G T G C C T C AGAT G G C AG GAG T G C C A GAGTCCCCTTTTTCTAGGACCGGAGAGGGCCTGGATATCAGGGGAACACAGGGCTTTCCA TGGGTGTCTC C AAG C C C AC CACAG C AG AG G C T G C C AC T G C T G GAG T G C AC C C C T C AG T C C C AG T C T GAGAG C AAG AAGAAC AG GAG G G GAG GAAG G GAG GAC AT C C T G GAGAAG T G GAT C AC C A C AAG AAG GAAG G C C G A G GAG C T G GAG A A G GAC C T G C G G A A G G C C AG A A A AAC AAT C AAGAAG C T G GAAGAT GAGAAC CCCTGGCTGG G C AAT AT CAT C G G CAT CAT C AGAAAAG G C A A G GAC G G C GAG G GAG C A C C T C C AG C AAAG C G G C C TAG A AC C GAC C AGAT G GAG AT C GAT T C C G G CACAG G C AAG C G G C C AC AC AAG TCTGGCTT C AC C GAC AAG GAG AGAG AG GA T C AC C G C C G GAGAAAG G C C C T G GAAAAC AAGAAGAAG C AA T AAG C T C C G G C G G C AAGAA C T G AGCAGAGAAGAAGAGGAGGAGCTGGGCAGACTGACCGTGGAGGACGAGGAGAGGCGCCGG AGAG T G G C AG GAC C C AGAAC AG G C GAT G T GAAC C T GAG C G GAG GAG GAC C TAG G G GAG C A C C AG GAG G C G G C T T C G T G C C AGAAT G GAG G G C G T G C C AGAG T C C C C C T T AC C AG GAC A G GAGAG G G C C T G G CAT C AG G G G C A A C AG G G C T T T C C C T G G G T C C G C C C T T C A C C AC C A

C AG C AG AGAC TGCCCCTGCTG GAAT G C AC AC C AC AG TGAT GAG AATTCC G T SEQ ID NO: 59 delta 10 protein

MASQSETRRGRRGTREETLE WITARKKAEELEKDLRKTRKTIKKLEEENPWLG

NIVGIIRKGKDGEGAPPAXRPRTDQMEVDSGPGKRPHKSGFTDKEREDHRRRKAL

ENKKKQLSAGGKILSKEEEEELRRLTDEDEERKRRVAGPR\ ^r GDVNPSRGGPRGAP

GGGFVPQMAGVPESPFSRTGEGLDIRGTQGFPWVSPSPPQQRLPLLECTPQSQSES

KK RRGGREDILEKWTTTRRKAEELE DLRKARKTIKKLEDENPWLGNIIGIIRKG

KDGEGAPPAKRPRTOQMEroSGTGKRPHKSGFTDKEREDHRRRKAI-E KKKQLS SGGKNLSREEEEELGRLTVEDEERRRRVAGPRTGDVNLSGGGPRGAPGGGFVPR MEGVPESPFTRTGEGLDIRGNQGFPWVRPSPPQQRLPLLECTPQ

SEQ ID NO: 60 Core 1 wt (C-gt-H)

GAT A T GA T C C G T AT AAGAAT T T G G C G C GAG C G T G GAAC T G C T GAG CT T TCTGC C GAG C GAT T T T T T TCC GAG C G T G C G C GAT C T G C T G GAT AC C G C GAG C G C G C T G T AT C G C GAT G C G C T G GAAAG C C C G GAAC AT T G C C C C C GAAC CAT C C G C G C T G C G C C AG G C GAT T C T G T G C T G G G G C GAAC T GAT GAC C C T G G C GAG C T G G G T G G G C AAC AAC C T G GAAGAT C C G G C G G C G C G C GAT C T G G T G G T GAAC A G T GAAC AC C AAC A G G G C C T GAAAA T C G C C AG C T G C T G T G G T T T CAT T TAG C T G C C T GAC C T T T G G C C G C G AAAC C G T G C T G G AAT T C T G G T GAG C T T TGGCGTGTGGAT TCGCACCCCGCCGGCGTATCGCCCGCCGAACGCGCCGAT TCTGAGC ACCCTGCCGGAAACCACCGTGGTGCGCCAGCGCGGCCGCGCGCCGCGCCGCCGCACCCCG AGCCCGCGCCGCCGCCGCAGCCAGAGCCCGCGCCGCCGCCGCAGCCAGAGCCCGGCGAGC CAGTGC

SEQ ID NO: 61 core 1 wt with restriction sites (HindlH /EcoRI)

A-UAG C T TGCA CCATGGAT AT T GAT C C G T AT AAAGAAT T T G G C G C GAG C G T G GAAC T G C T G AG CT T TCTGC C GAG C GAT T T T T T TCC GAG C G T G C G C GAT C T G C T G GAT AC C G C GAG C G C G C T G TAT C G C GAT G C G C T G GAAAG C C C G GAAC AT T G C AC C C C GAAC CAT AC C G C G C T G C G C C AG G C GAT TCTGTGCTGGGGC GAAC T GAT GAC C C T G G C GAG C T G G G T G G G C AAC AAC C T G GAAGAT C C G G C G G C G C G C GAT CTGGTGGT GAAC T AT G T GAAC AC C AAC AT G G G C C T GAAA AT T C G C C G C T G C T G T G G T T T CAT AT T G C T G C C T GAC C T T T G G C C G C G AA C C G T G C T G GAAT AT C T G G T GAG C T T T G G C G T G T G GAT T C G C AC C C C G C C G G C G T AT C G C C C G C C GAAC G C G C C GAT T C T GAG C AC C C T G C C G GAAAC C AC C G T G G T G C G C C AG C G C G G C C G C G C G C C G CGCCGCCGCACCCCGAGCCCGCGCCGCCGCCGCAGCCAGAGCCCGCGCCGCCGCCGCAGC CAGAG C C C G GC GAGC C AG TGCTGAT G G AT T C C G T

SEQ ID NO: 62 core 1 codon optimized

GA T AT T GAT C C C T A T AAG GAG T T T G GAG CCTCTGTG GAG C T G C T GAG T T T TCTGC CAT C C GAT T T C T T T C C C AG T G T C C GAGAC C T G C T G GAC AC C G C AAG C G C C C T G T AC AG G GAT G C A C T G GAG T C C C C A GAG C AC T G C AC C C C T A AC C A C AC A G C C C T GAG G C AG G C A T C C T G T G C T G G G G A GAG C T GAT GAC C C T G G C AAG CTGGG GGG C A A C AAT C T G GAG G A C C C T G C AG C A C G G GAT CTGGTGGT GAAT TAT G T GAAC AC AAAT AT G G G C C T GAAGAT C C G G C AG C T G C T G T G G T T C C AC AT C T C T T G C C T GAC C T T T G G C AG AGAG AC AG T G C T G GAG T AC C T G G T GAG C T TCGGCGTGTG GAT C AG GAC C C C AC C T G CAT AT AG G C C AC C AAAC G C AC C AAT C C T G T C C AC AC T G C CAGAG AC AAC AG T G G T G C G C CAGAG G G G AAG AG C AC C AC G GAG AAG GAC AC C T T C T C C AAG AC GAAG G C GAAG C CAGAG C C C C AG G C GAAGAC GAAG C C AG T C C C C AG C AAG C CAGTGC

SEQ ID NO: 63 core I codon optimized with restriction sites (HindlH /EcoRI)

A-UAG C T TGCA CCATGGAT AT T GAT C C C TAT AAG GAG T T T G GAG C C T C T G T G GAG C T G C T G AG T T T TCTGC CAT C C GAT T TCT T TCC C AG T G T C C GAGAC C T G C T G GAC AC C G C AAG C G C C C T G TAG AG G GAT G C AC T G GAG T C C C CAGAG C AC T G C AC C C C T AC C AC AC AG C C C T GAG G C AG G C AAT CCTGTGCTG G G GAG AG C T G A T GAC C C T G G C A A G C T G G G T G G G C A AC A A T C T G GAG GAC C C T G C AG C AC G G GAT CTGGTGGT GAAT T AT G T GAAC AC AAAT AT G G G C C T GAAG AT C C G G C AG C T G C T G T G G T T C C AC AT C T C T T G C C T GAC C T T T G G C A GAGA GAC A G T G C T G GAG T AC C T G G T GAG CT TCGGCGTGTG GA T C AG GAC C C C AC C T G CA AT AG G C C AC C AAAC G C AC C AAT C C T G T C C AC AC T G C C AG AGAC AAC AG T G G T G C G C CAGAG G G GAAG AG C AC C A CGGAGAAGGACACC T TCTCCAAGACGAAGGCGAAGCCAGAGCCCCAGGCGAAGACGAAGC

C AG T C C C C AG C AAG C C AG T G C TGAT GAG AAT T C C G T SEQ ID NO: 64 core 1 protein

MDIDPYKEFGASVELLSFLPSDFFPSVRDLLDTASALYRDALESPEHCTPNHTALR QAILCWGELMTLASWVGNNLEDPAARDLVVNYVNTlNMGLKIRQLLWFffl GRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRQRGRAPRRRTPSPRRR RSQSPRRRRSQSPASQC

SEQ ID NO: 65 Pre-C-gt-H wt

C AG C T G T T T C AT C T G T G C C GA AT T T T T T G C AG C T G C C C GAG C G T G C AG G C GAG C AAA CTGTGCCTGGGCTGGCTGTGG G G CAT G GAT AT T GAT C C G T AT AAGAAT T T G G C G C GAG C G T G G AAC T G C GAG C T T T C T G C C GAG C GAT T T T T T T C C GAG C G T G C G C GAT C T G C T G GAT AC C G C GAG C G C G C T G T AT C G C GAT G C G C T G GAAAG C C C G GAAGAT T G C AC C C C G AAC CAT ACCGCGCTGCGCCAGGCGAT TCTGTGCTGGGGCGAACTGATGACCCTGGCGAGCTGGGTG G G C AC AAC C T G G AAG AT C C G G C G G C G C G C G T C T G G T G G T GAAC TAT G T GAAC AC C AAC AT G G G C C T GAAAAT T C G C C AG CTGCTGTGGT T T CAT AT TAG C T G C C T GAC CT T TGGCCG C GAAAC C G T G C T G GAAT AT C T G G T GAG C T T T G G C G T G T G GAT T C G C AC C C C G C C G G C G TAT C G C C C G C C GAAC G C G C C GAT T C T GAG C A C C C T G C C G G AAA C C AC CGTGGTGC G C C G C G C GGCCGCGCGCCGCGCCGCCGCACCCCGAGCCCGCGCCGCCGCCGCAGCCAGAGCCCGCGC C G C C G C C G C A G C C A GAG C C C G G C GAG C C AG T G C

SEQ ID NO: 66 Pre-C-gt-H wt with restriction sites (Hindlll /EcoRI)

AJJAGCT T G CA C CAT GG C C C AG C T G T T T CAT C T G T G C C T GAT T AT T T T T T G C AG C T G C C C G ACCGTGCAGGCGAGCAAACTGTGCCTGGGCTGGCTGTGGGGCATGGATATTGATCCGTAT AAAGAAT T T G G C G C G A G C G T G G A A C T G C T GAG CT T TCTGCC GAG C GAT T T T T T TCC GAG C G T G C G C GAT C T G C T G GAT AC C G C GAG C G C G C T G T AT C G C GAT G C G C T G GAAAG C C C G GAA C A T T G C AC C C C G A A C CAT AC C G C G C T G C G C C AG G C GAT T C T G T G C T G G G G C G A A C T G A T G AC C C T G G C GAG C T G G G T G G G C AAC AAC C T G GAAGAT CCGGCGGC G C G C GAT C T G G T G G T G AAC TAT G T GAAC AC C AAC AT G G G C C T GAAAAT T C G C C AG C T G C T G T G G T T T CAT AT TAG C T G C C T GAC C T T T G G C C G C G AAA C C G T G C T G GAAT AT C T G G T GAG C T T T G G C G T G T G G T T C G C AC C C C G C C G G C G T AT C G C C C G C C GAAC G C G C C GAT T C T GAG C AC C C T G C C G GAAAC C ACCGTGGTGCGCCAGCGCGGCCGCGCGCCGCGCCGCCGCACCCCGAGCCCGCGCCGCCGC

C G C AG C C AG AG C C C G C G C C G C C G C C G C AG C C AG AG C C C G G C GAG C C AG T G C T GAT GAG U A AT TCCGT

SEQ ID NO: 67 Pre-C-gt-H codon optimized

G C C C AG C T G T T T CAT CTGTGCC GA TAT T T TCTGT T CAT G C C C TAG C G T C C AG G C T T C T AAAC T G T G C C T G G G G T G G C T G T G G G GAAT G GAC AT C GAT C C C T AC AAG GAG T T C G G C G C C AG C G T G GAG C T G C T GAG C T T T C T G C C C T C C GAC T T C T T T C C T T C T G T G C G G GAC C T G C T G GAT AC C G C AAG C G C C C T G T AT AGAGAT G C AC T G GAG T C C C C AGAG C AC T G C AC C C C AAAC C AC AC AG C C C T GAG G C AG G C AAT C C T G T G C T G G G GAG AG C T GAT GAC C C T G G CAT C C T G G G T G G G C AAC AA C T G GAG GAC CCTGCCGC C AGAG A C T G G T G G T GAA T AC G T GAAC AC A AAT AT G G G C C T GAAGAT C AG G C AG CTGCTGTGGT TC C AC AT CTCT TGCCT GAC C T T T G G C C G C GAG AC AG T G C T G GAG T A C C T G G T G A G C T T C G G C G T G T G GAT C AG GAC C C C AC C T G C A T A T AG G C C AC C AAAC G C AC C T A T C C T G T C C AC AC T G C C AGAG AC AAC AG T G G T G C G C C AG AG G G G AAG AG C AC C AC G GAG AAG GAC AC C T T C T C C AAG GAG GAG AAG AAG C C AG T C C C C A C GAAGAAGAC GAAGC CAGAGC C CAG C CAG C CAG T G T

SEQ ID NO: 68 Pre-C-gt-H codon optimized with restriction sites (Hindlll /EcoRI)

AHAG C T T GCA CCATGG C C CAG C T G T T T C AT C T G G C C GA T T AT T T T C T G T T CAT G C C C T AC C G T C CAG G C T T C AAAC T G T G C C T G G G G T G G C T G T G G G GAAT G GAC AT C GAT C C C TAG A A G GAG T T C G G C G C C AG C G T G G AG C T G C T G AG C T T T C T G C C C T C C G AC T T C T T T C C T T C T G T G C G G GAC C T G C T G GAT AC C G C AAG C G C C C T G T AT AGAGAT G C AC G GAG T C C C C AGAG C AC T G C AC C C C A AC C AC AC AG C C C T G G G C G G C AT C C T G G C T G G G GAG AG C T GAT G AC C C T G G C AT C C T G G G T G G G C A AC A A T C T G GAG GAC C C T G C C G C C A GAGA CTGGTGGTG AAT T AC G T GAAC AC AAT AT G G G C C T GAAGAT C AG G C AG CTGCTGTGGTTC C AC AT C T C T T G C C T GAC C T T T G G C C G C G A GAC A G T G C T G G A G T AC C T G G T GAG C T T C G G C G T G T G GAT C AG GAC C C C AC C T G CAT AT AG G C C AC C AAC G C AC C TAT C C T G T C C AC AC T G C C AGAGAC A AC AG T G G T G C G C C AG AG G G G AG AG C AC C AC G GAG AAG GAC AC C T T C T C C AG GAG GAGA

AGAAG C C AG T C C C C AC GAAGAAG AC GAAG C C AGAG C C C AG C C AG C C AG T G T TGAT GAGUA ATTCCGT

SEQ ID NO: 69 Pre-C-gt-H protein

MAQLFHLCLIIFCSCPTVQASKLCLGWLWGMDIDPYKEFGASVELLSFLPSDFFPS VRDLLDTASALYRDALESPEHCTPNHTALRQAILCW

ARDLVWYVNmMGLKIRQUAVFHISCLTFGRETVTE^lA^SFG IRTPPAYRPP NAPILSTLPETTVVRQRGRAPRRRTPSPRRRRSQSPRRRRSQSPASQC

SEQ ID NO: 70 PreC-C-Mut-gt-H wt

C AG C T G T T T CAT CTGTGCCT GAT TZATTTTTTG C AG C T G C C C GAC C T T T C AG T T T C C GAAA CTGTGCCTGGGCTGGCTGTGGGGCATGGATATTGATCCGTATAAAGAATTTGGCGCGAGC G T G GAAC T G C T GAG CTTTCTGCC GAG C GAT TTTTTTCC GAG C G T G C G C GA T C T G C T G GAT AC C G C GAG C G C G C T G TAT C G C GAT G C G C T G G AAAG C C C G GAAC A T G C AC C C C GAAC CAT AC C G C G C T G C G C C AG G C GAT T C T G T G C T G G G G C G A A C T G A T GAC C C T G G C G A G C T G G G T G G G C AAC AC C T G GAAGAT C C GGCGGCGCGC GAT C T G G T G G T GAAC T AT G T GAAC AC C AAC AT G G G C C T GAAAAT T C G C C AG C T G C T G T G G T T T CAT AT TAG C T G C C T GAC C T T T G G C C G C GAAAC C G T G C T G GAA T C T G G T GAG C T T T G G C G T G T G GA T T C G C AC C C C G C C G G C G TAT C G C C C G C C GAAC G C G C C GAT T C T GAG C AC C C T G C C G GAAA C C AC CGTGGTGCGC C AG C G C GGCCGCGCGCCGCGCCGCCGCACCCCGAGCCCGCGCCGCCGCCGCAGCCAGAGCCCGCGC C G C C G C C G C AG C C AG A G C C C G G C GAG C C AG T G C

SEQ ID NO: 71 PreC-C-Mut-gt-H wt with restriction sites (Hindlll /EcoRI)

A AGCTTGCACC¾TGGCCCAGCTGTTTCATCTGTGCCTGATTATTTTTTGCAGCTGCCCG AC C T T T C AG T T T C C GAAAC TGTGCCTGGGCTGGCTGTGGGG CAT G GAT AT T GAT C C G TAT AAAGAAT T T G G C G C GAG C G T G GAAC T G C T GAG CTTTCTGC C GAG C GAT TTTTTTCC GAG C G T G C G C GAT C T G C T G GAT AC C G C GAG C G C G C T G TAT C G C GAT G C G C T G GAAAG C C C G G AA CAT T G C AC C C C GAAC CAT AC CGCGCTGCGC C AG G C GAT TCTGTGCTGGGGC GAAC T GAT G ACCCTGGCGAGCTGGGTGGGCAACAACCTGGAAGATCCGGCGGCGCGCGATCTGGTGGTG AAC TAT G T GAACAC C AAC AT G G G C C T GAAAAT T C G C CAG C T GC T G T G G T T T CAT AT T AG C T G C C T GAC CTTTGGCCG C GAAAC C G T G C T G GAAT AT C T G G T GAG CTTTGGCGTGTG GAT T C G C AC C C C G C C G G C G TAT C G C C C G C C GAAC G C G C C GAT T C T GAG C AC C C T G C C G GAAAC C ACCGTGGTGCGCCAGCGCGGCCGCGCGCCGCGCCGCCGCACCCCGAGCCCGCGCCGCCGC CGCAGCCAGAGCCCGCGCCGCCGCCGCAGCCAGAGCCCGGCGAGCCAGTGCTGATGAG A

ATTCCGT

SEQ ID NO: 72 PreC-C-Mut-gt-H codon optimized

GCCCAGCTGTTTCATCTGTGCCTGATTATTTTCTGTTCATGCCCTACCTTCCAGTTCCCC AAAC T G T G C C T G G G G T G G C T G T G G G GAAT G GAC A T C GA T C C C T AC AAG GAG T T C G G C G C C AGCGTGGAGCTGCTGAGCTTTCTGCCCTCCGACTTCTTTCCTTCTGTGCGGGACCTGCTG GAT AC C G C AAG C G C C C T G TAT AGAG AT G C AC T G GAG T C C C C AGAG C AC T G C AC C C C AAAC C A C AC A G C C C T GAG G CAG G C A A TCCTGTGCTGGG GAGA G C G G A C C C T G G C A T C C T G G G T G G G C AAC AAT C T G GAG GAC CCTGCCGC C AGAG AT CTGGTGGT GAAT T AC G T G AAC AC A AAT AT G G G C C T GAAGAT C AG G C AG CTGCTGTGGT TC C AC AT CTCT TGCCT GAC C T T T G G C C G C GAG AC AG T G C T G GAG T A C C G G T G A G C T C G G C G T G T G GAT C AG GAC C C C AC C T G C A T A T AG G C C AC C AAAC G C AC C T A T C C T G T C C AC AC T G C C AGAG AC AAC AG T G G T G C G C C AG AG G G G AAG AG C AC C AC G G AG AAG GAC AC C T T C T C C AAG GAG G AG AAG AAG C C AG T C C C C A C GAAGAAGAC GAAGC CAGAGC C CAG C CAG C CAG T G T

SEQ ID NO: 73 PreC-C-Mut-gt-H codon optimized with restriction sites (Hindlll /EcoRI)

A AG C T TGCACCATGG C C CAG C T G T T T C AT C T G T G C C T GA T T AT T T T C T G T T CAT G C C C T AC C T T C CAG T T C C C C AAAC T G T G C C T G G G G T G G C T G T G G G GAAT G GAC AT C GAT C C C T AC A A G GAG T T C G G C G C C AG C G T G G AG C T G C T G AG C T T T C T G C C C T C C G AC T T C T T T C C T T C T G T G C G G GAC C T G C T G GAT AC C G C AAG C G C C C T G TAT AGAGAT G C AC T G GAG T C C C C AGAG C AC T G C AC C C C AAAC C AC AC AG C C C T G A G G C A G G C A AT C C T G T G C T G G G GAG AG C T GAT G AC C C T G G CAT C CTGGGTGG G C AAC AAT C T G GAG GAC C C T G C C G C C AGAGAT CTGGTGGTG AAT T AC G T GAAC AC AAT AT G G G C C T GAAGAT CAG G CAG CTGCTGTGGT TC C AC AT C T C T T G C C T GAC CT T TGGCC G C G A GAC A G T G C T G G A G T AC C T G G T GAG CT TCGGCGTGTG GAT C AG GAC C C C AC C T G CAT AT AG G C C AC C AAC G C AC C TAT C C T G T C C AC AC T G C C AGAGAC A ACAGTGGTGCGCCAGAGGGGAAGAGCACCACGGAGAAGGACACCT TCTCCAAGGAGGAGA

AGAAG C CAG T C C C C AC GAAGAAG AC GAAG C C AGAG C C CAG C CAG C CAG T G T TGAT GAGUA AT TCCGT

SEQ ID NO: 74 PreC-C-Mut-gt-H protein

MAQLFHLCLIIFCSCPTFQFPKLCLGWLWG-MDIDPYKEFGASVELLSFLPSDFFPSV RDLLDTASALYRDALESPEHCTPNHTALRQAILCWGELMTLASWVGNNLEDPAA

RDLVVNYVNTNMGLKniQLLWFffiS^

APIL S TLPETT WRQRGRAPRRRTP SPRPvRRS Q SPRRRRS Q SP AS QC