COMPOSITIONS AND METHODS FOR MUCOSAL VACCINATION AGAINST

SARS-COV-2

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Patent Application No. 62/981873, filed on February 26, 2020, which is incorporated by reference herein in its entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH [0002] This invention was made with government support under 1R21AI130712A and R01AI146063A awarded by the National Institutes of Health and under 5880429024 awarded by the United States Department of Agriculture - Agricultural Research Service. The Government has certain rights in the invention.

BACKGROUND

[0003] COVID-19, the disease caused by the virus SARS-CoV-2, is extremely infectious and sustainable in the community. The virus spreads mainly through respiratory droplets, possible aerosol, produced when an infected person coughs or sneezes. These droplets or aerosols can land in the mouths or noses of people who are nearby or possibly inhaled into the lungs. The highly contagious nature is probably due to the virus spreading via asymptomatic patients. Although most patients are not severe, the virus can cause acute, highly lethal pneumonia with a 2-10 day incubation period in the elderly or people underlying medical conditions. Although children infected with SARS-CoV-2 have less symptoms, they can spread the virus easily to others. The SARS-CoV-2 virus infects respiratory epithelial cells through its Spike (S) binding to angiotensin-converting enzyme 2 (ACE2) receptor. Using Spike (S) protein, the SARS-CoV-2 virus binds to ACE2 receptor in nasal, bronchial, alveolar, and other epithelial cells. During infection, the S protein is cleaved into SI and S2 subunits by host proteases. SI mainly contains the receptor-binding domain (RBD) which allows viruses to directly bind to the ACE2, S2 likely mediates membrane fusion with the help of a protease TMPRSS2 in cells.

[0004] The neonatal Fc Receptor (FcRn) plays a crucial role in transporting IgG antibody across the polarized epithelial cells lining the respiratory, intestinal, genital tract and the placenta. FcRn expresses in cell surface or resides within low-pH endosomes. Normally, IgG enters cells via pinocytotic vesicles that fuse with endosomes. IgG which binds to FcRn is transported to the basolateral surface and released into the submucosa. It has been shown that FcRn in dendritic cells (DCs) and macrophages enhances antigen presentation to CD4 T helper, or cross-presentation to CD8 T cells. FcRn in all mammals are structurally and functionally similar.

[0005] Presently, most vaccines against respiratory infections are designed for delivery via the muscle or skin but are intended to protect the lung. Parenteral delivery elicits relatively poor immunity in the respiratory tract even though they often induce robust systemic immunity. A partial reason is that parenteral immunization fails to induce strong mucosal antibody and cell- mediated immunity including T and B cells that reside in the lung. Since SARS-CoV-2 viruses infect the upper or lower respiratory tract and asymptomatic infections frequently occur, the development of a safe and effective mucosal vaccine to prevent the infection and possibly reinfection in the long term is urgently needed. Ideally, a mucosal vaccine mimics the route of natural viral exposure and engenders beneficial nasal and lung immunity. This goal can be best achieved by direct delivery of the SARS-CoV-2 vaccine antigen via the intranasal route.

BRIEF SUMMARY

[0006] Described herein are compositions and methods for using the FcRn to deliver SARS- CoV-2 spike antigens to induce protective immunity against SARS-CoV-2 virus infection.

[0007] Disclosed are peptides comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; SARS-CoV-2 antigen; and a trimerization domain. In some aspects, the SARS-CoV-2 antigen can be a SARS-CoV-2 spike protein. Thus, disclosed are peptides comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; SARS- CoV-2 spike protein; and a trimerization domain.

[0008] Disclosed are peptide complexes comprising three of the disclosed peptides. For example, disclosed are peptide complexes comprising three peptides, wherein each of the three peptides comprises a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; SARS-CoV-2 antigen; and a trimerization domain.

[0009] Disclosed are nucleic acid sequences capable of encoding any of the peptides disclosed herein.

[0010] Disclosed are compositions comprising any of the disclosed peptides, peptide complexes, nucleic acid sequences, or vectors. In some instances, disclosed are compositions comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS- CoV-2 antigen; and a trimerization domain.

[0011] Disclosed are methods for eliciting a protective immune response against SARS- CoV-2 comprising administering to a subject an effective amount of a composition comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS-CoV-2 antigen; and a trimerization domain, wherein the administering is to a mucosal epithelium.

[0012] Disclosed are methods of treating a subject exposed to SARS-CoV-2 or at risk of being exposed to SARS-CoV-2 comprising administering to a subject an effective amount of a composition comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS-CoV-2 antigen; and a trimerization domain, wherein the administering is to a mucosal epithelium.

[0013] Disclosed are methods of reducing SARS-CoV-2 viral titers in a subject infected with SARS-CoV-2 comprising administering to a subject an effective amount of a composition comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS- CoV-2 antigen; and a trimerization domain, wherein the administering is to a mucosal epithelium.

[0014] Additional advantages of the disclosed method and compositions will be set forth in part in the description which follows, and in part will be understood from the description, or may be learned by practice of the disclosed method and compositions. The advantages of the disclosed method and compositions will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed.

BRIEF DESCRIPTION OF THE DRAWINGS [0015] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments of the disclosed method and compositions and together with the description, serve to explain the principles of the disclosed method and compositions.

[0016] FIG. 1 shows a schematic representing a proposed model of FcRn-mediated transfer of SARS-CoV-2 vaccine antigens across a respiratory epithelial barrier and target to mucosal antigen presenting cells (APCs) (e.g. dendritic cells) and B cells.

[0017] FIG. 2 shows a schematic illustration of the fusion of S, SI, RBD, the foldon, and Fey cDNA to create a trimeric S-Fc fusion gene. S, Spike; SP, signal peptide; RBD, receptor binding domain; FP, fusion peptide; TM, transmembrane domain. Fd; Foldon domain, cleavage site; R816A, mutation at S2’ cleavage site; K986P/V987P, mutation keeping pre-fusion structure; C226S/C229S, mutation for a monomer hlgGl; K322A, mutation.

[0018] FIG. 3 shows a protein gel demonstrating the production of SARS-CoV-2 S, S-Fc, Sl-Fc, and RBD-Fc fusion proteins. CHO or 293T cells were transfected with plasmids encoding S, S-Fc/wt, Sl-Fc/wt, or RBD-Fc/wt. The stable cell lines were selected and cloned. The proteins in supernatants were purified with anti-His beads for S antigen or Protein A/G- agarose beads. The purified proteins were detected by Commassie blue.

[0019] FIG. 4 shows that intranasal immunization of mice with S-Fc, Sl-Fc or RBD-Fc induced S-specific antibody immune responses. Top panel : Intranasal delivery of both Sl-Fc or RBD-Fc antigens induces Spike-specific antibody immune responses. Five pg of purified spike Sl-Fc, RBD-Fc, or PBS in combination with 10 pg of CpG were intranasally (i.n.) administered into mouse (n=5). Spike-specific antibody titers in sera were measured 14 days after boost by ELISA. The data represent mean ± S.E.M. Bottom panel. SARS-CoV-2 neutralization by serum antibodies. Neutralization assays were performed by incubating SARS-CoV-2 pseudoviruses (50 ul) with 1:10 dilution of the pooled mouse sera at 37°C for 1 hr. After incubation, the 100 pL of the sera-pseudovirus mixture were added to ACE2/293T cells. After 72 hr incubation, luciferase activity was measured using luciferin-containing substrate. Controls included cell-only control, virus without any antibody control. The PBS immunized mice serum as a negative control. The average percentage inhibition (at 1:10 serum dilution) for each group are shown. Data is shown for 5 mice per group.

[0020] FIG. 5 shows the immune response is FcRn-dependent. Top. S-specific IgG titers in sera were measured by ELISA 14 days after boosting. Bottom. The neutralization antibody titers in the sera were expressed as the reciprocal of the twofold serial dilution preventing the appearance of the cytopathogenic effect (CPE) in Vero E6 cells. KO: FcRn knockout mice [0021] FIG. 6 shows the mean survival following viral challenge. Two weeks after the boost, groups of 5 mice were i.n. challenged with SARS-CoV-2 virus and weighed daily for 14 days. Mice were humanely euthanized if above 25% of initial body weight was lost. The percentage of mice from protection after the challenge was shown by the Kaplan-Meier survival curve.

[0022] FIG. 7 shows the mean of viral titers following viral challenge. The virus titers in the different organs of the mice (n=3) were determined 5 days after challenge. Supernatants of the tissue homogenates were added onto Vero E6 and incubated for three days. The viral titers were measured by 50% reduction of CPE.

[0023] FIG. 8 shows an example of the histopathology of the lungs from the infected or normal mice. Lungs were collected from day 5 post challenge. The sections were stained with H & E to determine the level of inflammation (lOx). The representative slides were shown.

[0024] FIG. 9 shows a schematic illustration of the fusion of S, SI, RBD, the foldon, and Fey cDNA to create a trimeric S-Fc fusion gene and further includes a RBD-Fc fragment fusion without a trimerization domain. S, Spike; SP, signal peptide; RBD, receptor binding domain; FP, fusion peptide; TM, transmembrane domain. Fd; Foldon domain, cleavage site; R816A, mutation at S2’ cleavage site.

[0025] FIG. 10 shows a schematic illustration of an FcRn-mediated delivery of SARS-CoV- 2 vaccine antigens.

DETAILED DESCRIPTION

[0026] The disclosed method and compositions may be understood more readily by reference to the following detailed description of particular embodiments and the Example included therein and to the Figures and their previous and following description.

[0027] It is to be understood that the disclosed method and compositions are not limited to specific synthetic methods, specific analytical techniques, or to particular reagents unless otherwise specified, and, as such, may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0028] Disclosed are materials, compositions, and components that can be used for, can be used in conjunction with, can be used in preparation for, or are products of the disclosed method and compositions. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds may not be explicitly disclosed, each is specifically contemplated and described herein. For example, if a peptide is disclosed and discussed and a number of modifications that can be made to a number of molecules including the amino acids are discussed, each and every combination and permutation of peptide and the modifications that are possible are specifically contemplated unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A-D is disclosed, then even if each is not individually recited, each is individually and collectively contemplated. Thus, is this example, each of the combinations A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are specifically contemplated and should be considered disclosed from disclosure of A, B, and C; D, E, and F; and the example combination A-D. Likewise, any subset or combination of these is also specifically contemplated and disclosed. Thus, for example, the sub-group of A-E, B-F, and C-E are specifically contemplated and should be considered disclosed from disclosure of A, B, and C; D, E, and F; and the example combination A-D. This concept applies to all aspects of this application including, but not limited to, steps in methods of making and using the disclosed compositions. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific embodiment or combination of embodiments of the disclosed methods, and that each such combination is specifically contemplated and should be considered disclosed.

A. Definitions

[0029] It is understood that the disclosed method and compositions are not limited to the particular methodology, protocols, and reagents described as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims.

[0030] It must be noted that as used herein and in the appended claims, the singular forms "a ", "an", and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, reference to "a peptide" includes a plurality of such peptides, reference to "the composition" is a reference to one or more compositions and equivalents thereof known to those skilled in the art, and so forth.

[0031] As used herein, the term "therapeutically effective amount" means an amount of a therapeutic, prophylactic, and/or diagnostic agent that is sufficient, when administered to a subject suffering from or susceptible to a disease, disorder, and/or condition, to treat, alleviate, ameliorate, relieve, alleviate symptoms of, prevent, delay onset of, inhibit progression of, reduce severity of, and/or reduce incidence of the disease, disorder, and/or condition.

[0032] As used herein, the term "treating" refers to partially or completely alleviating, ameliorating, relieving, delaying onset of, inhibiting progression of, reducing severity of, and/or reducing incidence of one or more symptoms or features of a particular disease, disorder, and/or condition (e.g. SARS-CoV-2 infection). For example, "treating" SARS-CoV-2 may refer to inhibiting survival, growth, and/or spread of the virus. Treatment may be administered to a subject who does not exhibit signs of a disease, disorder, and/or condition and/or to a subject who exhibits only early signs of a disease, disorder, and/or condition for the purpose of decreasing the risk of developing pathology associated with the disease, disorder, and/or condition.

[0033] As used herein, “subject” refers to the target of administration, e.g. an animal. Thus the subject of the disclosed methods can be a vertebrate, such as a mammal. For example, the subject can be a human. The term does not denote a particular age or sex. Subject can be used interchangeably with “individual” or “patient”.

[0034] The term ‘peptide’ refers to a polymer of amino acids and does not refer to a specific length of the product; thus, polypeptides, oligopeptides, and proteins are included within the definition of peptide. This term also does not refer to or exclude post-expression modifications of the peptide, for example, glycosylations, acetylations, phosphorylations and the like. Included within the definition are, for example, peptides containing one or more analogues of an amino acid (including, for example, unnatural amino acids, PNA, etc.), peptides with substituted linkages, as well as other modifications known in the art, both naturally occurring and non- naturally occurring.

[0035] The term ‘promoter’ is a nucleotide sequence which is comprised of consensus sequences which allow the binding of RNA polymerase to the DNA template in a manner such that mRNA production initiates at the normal transcription initiation site for the adjacent structural gene.

[0036] The expression ‘operably linked’ refers to a juxtaposition wherein the components so described are in a relationship permitting them to function in their intended manner. A control sequence ‘operably linked’ to a coding sequence is ligated in such a way that expression of the coding sequence is achieved under conditions compatible with the control sequences.

[0037] “Optional” or “optionally” means that the subsequently described event, circumstance, or material may or may not occur or be present, and that the description includes instances where the event, circumstance, or material occurs or is present and instances where it does not occur or is not present.

[0038] Ranges may be expressed herein as from "about" one particular value, and/or to "about" another particular value. When such a range is expressed, also specifically contemplated and considered disclosed is the range from the one particular value and/or to the other particular value unless the context specifically indicates otherwise. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another, specifically contemplated embodiment that should be considered disclosed unless the context specifically indicates otherwise. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint unless the context specifically indicates otherwise. Finally, it should be understood that all of the individual values and sub-ranges of values contained within an explicitly disclosed range are also specifically contemplated and should be considered disclosed unless the context specifically indicates otherwise. The foregoing applies regardless of whether in particular cases some or all of these embodiments are explicitly disclosed.

[0039] As used herein, “coronavirus” refers to a group of RNA viruses of the subfamily Orthocoronavirinae, in the family Coronaviridae, order Nidovirales, and realm Riboviria. They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses ranges from approximately 26 to 32 kilobases, one of the largest among RNA viruses. They have characteristic club-shaped spikes that project from their surface, which in electron micrographs create an image reminiscent of the solar corona, from which their name derives. In some aspects, the coronavirus is Middle East respiratory syndrome coronavirus (MERS-CoV), Human Coronavirus — Erasmus Medical Centre (HCoV-EMC), SARS-CoV, or SARS-CoV-2.

[0040] The term “subject” refers to the target of administration, e.g. an animal. Thus, the subject of the disclosed methods can be a vertebrate, such as a mammal. For example, the subject can be a human. The term does not denote a particular age or sex. Subject can be used interchangeably with “individual” or “patient.” For example, the subject of administration can mean the recipient of the alternating electrical field.

[0041] By “prevent” is meant to minimize or decrease the chance that a subject will develop a coronavirus infection.

[0042] As used herein, the terms “administering” and “administration” refer to any method of providing a therapeutic, such as an antiviral agent or coronavirus therapeutic (e.g., a peptide or peptide complex as disclosed herein), to a subject. Such methods are well known to those skilled in the art and include, but are not limited to: oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intravaginal administration, ophthalmic administration, intramural administration, intracerebral administration, rectal administration, sublingual administration, buccal administration, and parenteral administration, including injectable such as intravenous administration, intra-arterial administration, intramuscular administration, and subcutaneous administration. Administration can be continuous or intermittent. In various aspects, a preparation can be administered therapeutically; that is, administered to treat an existing disease or condition. In further various aspects, a preparation can be administered prophylactically; that is, administered for prevention of a disease or condition. In an aspect, the skilled person can determine an efficacious dose, an efficacious schedule, or an efficacious route of administration so as to treat a subject. In some aspects, administering comprises exposing. Thus, in some aspects, exposing a subject to alternating electrical fields means administering alternating electrical fields to the subject.

[0043] “Optional” or “optionally” means that the subsequently described event, circumstance, or material may or may not occur or be present, and that the description includes instances where the event, circumstance, or material occurs or is present and instances where it does not occur or is not present.

[0044] Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of skill in the art to which the disclosed method and compositions belong. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present method and compositions, the particularly useful methods, devices, and materials are as described. Publications cited herein and the material for which they are cited are hereby specifically incorporated by reference. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such disclosure by virtue of prior invention. No admission is made that any reference constitutes prior art. The discussion of references states what their authors assert, and applicants reserve the right to challenge the accuracy and pertinency of the cited documents. It will be clearly understood that, although a number of publications are referred to herein, such reference does not constitute an admission that any of these documents forms part of the common general knowledge in the art.

[0045] Throughout the description and claims of this specification, the word “comprise” and variations of the word, such as “comprising” and “comprises,” means “including but not limited to,” and is not intended to exclude, for example, other additives, components, integers or steps. In particular, in methods stated as comprising one or more steps or operations it is specifically contemplated that each step comprises what is listed (unless that step includes a limiting term such as “consisting of’), meaning that each step is not intended to exclude, for example, other additives, components, integers or steps that are not listed in the step.

B. Coronaviruses

[0046] Coronaviruses are a group of RNA viruses that cause diseases in mammals and birds. In humans and birds, they cause respiratory tract infections that can range from mild to lethal. Mild illnesses in humans include some cases of the common cold (which is also caused by other viruses, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS, and COVID-19. In cows and pigs they cause diarrhea, while in mice they cause hepatitis and encephalomyelitis.

[0047] Coronaviruses are members of the subfamily Orthocoronavirinae, in the family Coronaviridae, order Nidovirales, and realm Riboviria. They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses ranges from approximately 26 to 32 kilobases, one of the largest among RNA viruses. They have characteristic club-shaped spikes that project from their surface, which in electron micrographs create an image reminiscent of the solar corona, from which their name derives.

[0048] Over the past two decades, emerging pathogenic coronaviruses capable of causing life-threatening disease in humans and animals have been identified, namely severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). In December 2019, the Wuhan Municipal Health Committee (Wuhan, China) identified an outbreak of viral pneumonia cases of unknown cause. Coronavirus RNA was identified in some of these patients. This novel coronavirus has been named SARS- CoV-2, and the disease caused by this virus has been named COVID-19. Currently there are approximately 50 million confirmed cases of COVID-19 and over 1.2 million deaths globally. [0049] Individuals of all ages are at risk for infection and severe disease. However, the probability of serious COVID-19 disease is higher in people aged >60 years, those living in a nursing home or long-term care facility, and those with chronic medical conditions. The spectrum of illness can range from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome (ARDS) and death. Although COVID-19 patients can present with many different symptoms the main symptoms are fever, cough or shortness of breath. The abnormalities seen in chest X-rays vary, but bilateral multi-focal opacities are the most common. The abnormalities seen in computed tomography (CT) of the chest also vary, but the most common are bilateral peripheral ground-glass opacities, with areas of consolidation developing later in the clinical course. In the early phase of the disease and in an asymptomatic presentation the imaging of both X-ray and CT can be normal. Virologic testing (i.e., using a molecular diagnostic or antigen test to detect SARS-CoV -2) is recommended by the NIH for diagnosing SARS-CoV-2 in patients with suspected COVID-19 symptoms.

[0050] COVID-19 patients can be grouped into the following groups by illness severity - asymptomatic or presymptomatic, mild, moderate, severe and critical illness, where patients with severe illness are individuals who have respiratory frequency >30 breaths per minute, Sp02 <94% on room air at sea level, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (Pa02/Fi02) <300 mmHg, or lung infiltrates >50%. The management of a COVID-19 patient with severe illness includes pulmonary imagining and ECG, if indicated. Laboratory evaluation includes a complete blood count (CBC) with differential and a metabolic profile, including liver and renal function tests. Measurements of inflammatory markers such as C- reactive protein (CRP), D-dimer, and ferritin, while not part of standard care, may have prognostic value.

[0051] Although it has been almost a year since the first case of COVID-19 pneumonia, current treatment options are limited and involve the treatment of symptoms, supportive care, isolation, and experimental measures. Therefore, there is an urgent unmet need to develop new therapies for the treatment of COVID-19 and other coronavirus infections. C. Peptides

1. Peptides comprising a trimerization domain [0052] Disclosed are peptides comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a coronavirus antigen; and a trimerization domain. In some aspects, the coronavirus antigen can be any coronavirus spike protein, or antigenic fragment thereof. In some aspects, the coronavirus is Middle East respiratory syndrome coronavirus (MERS-CoV), Human Coronavirus — Erasmus Medical Centre (HCoV-EMC), SARS-CoV, or SARS-CoV-2. Thus, in some aspects, the coronavirus spike protein can be a MERS-CoV, HCoV-EMC, SARS- CoV, or SARS-CoV-2 spike protein, or antigenic fragment thereof.

[0053] Disclosed are peptides comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; SARS-CoV-2 antigen; and a trimerization domain. In some aspects, the SARS-CoV-2 antigen can be a SARS-CoV-2 spike protein. Thus, disclosed are peptides comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; SARS- CoV-2 spike protein; and a trimerization domain.

[0054] In some instances, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn is conjugated to the amino or carboxy terminal end of a trimerization domain. In some aspects, the SARS-CoV-2 antigen is conjugated to the amino or carboxy terminal end of a trimerization domain. In some aspects, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn is conjugated to the C-terminal end of a trimerization domain and the N- terminal end of the trimerization domain is conjugated to the C-terminal end of the SARS-CoV- 2 antigen. In some instances, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn is conjugated to the amino or carboxy terminal end of a SARS-CoV-2 antigen.

[0055] As described herein, the disclosed peptides can comprise a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a coronavirus antigen; and a trimerization domain. In some aspects, the order, from the N-terminus to the C-terminus of the peptide can be 1) coronavirus antigen, trimerization domain, monomeric Fc fragment of an immunoglobulin recognized by a FcRn; 2) monomeric Fc fragment of an immunoglobulin recognized by a FcRn, trimerization domain, coronavirus antigen; or 3) monomeric Fc fragment of an immunoglobulin recognized by a FcRn, coronavirus antigen, trimerization domain.

[0056] The conjugation can be direct or indirect. Indirect conjugation can be due to the presence of a linker, for example, a linker can be present in between the SARS-CoV-2 antigen and a trimerization domain.

[0057] Disclosed are peptides encoded by one or more of the nucleic acid sequences provided herein. i. Monomeric Fc Fragment

[0058] A monomeric Fc fragment of an immunoglobulin recognized by a FcRn, as disclosed herein, can be any Fc fragment that can be recognized by a FcRn. In some aspects, monomeric Fc fragment of an immunoglobulin recognized by a FcRn can comprise only the Fc portion of an immunoglobulin.

[0059] The disclosed monomeric Fc fragments of an immunoglobulin recognized by a FcRn are altered or mutated in order to make them monomeric. The monomeric Fc fragments of an immunoglobulin recognized by a FcRn cannot form dimers as found in an antibody. In some instances the monomeric Fc fragment of an immunoglobulin comprises a mutation in the Fc region of an immunoglobulin recognized by FcRn sequence that results in the prevention of dimer formation. In some aspects, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn comprises at least one mutation in a cysteine residue responsible for dimer formation. For example, mutations can be at one or more of positions 226 and 229 of the full length sequence of the wild type sequence of human IgGl. In some aspects, the Cys at positions 226 and 229 of full length human wild type IgGl can be mutated to Ser in order to prevent dimer formation. In some aspects, the cysteine mutations to serine can be found at positions 11 and 14 of a sequence comprising only the hinge region, CH2 and CH3 domains of wild type IgG. For example, the cysteine mutations to serine can be found at positions 11 and 14 of SEQ ID NO:7. In some aspects, positions 11 and 14 of SEQ ID NO:7 are located in the hinge region of monomeric Fc fragments of an immunoglobulin recognized by a FcRn.

[0060] In some instances, corresponding mutations can be made in other IgG Fc fragments and Fc fragments from other isotypes in order to mutate the cysteine residues responsible for dimer formation. In some instances, other mutations can be made throughout the Fc fragment of an immunoglobulin recognized by a FcRn so long as the FcRn binding region is not affected. [0061] In some aspects, the Clq binding site can be ablated in the monomeric Fc fragment. This can be effective to help avoid clearance of the Fc fragments via the complement pathway and thus allowing the disclosed peptides comprising a monomeric Fc fragment to remain in a subject and provide their therapeutic effect. In some aspects, Clq is known to bind to the CH2 domain of an immunoglobulin, particularly IgG. In some aspects, substituting the lysine at position 322 can ablate or eliminate the complement Clq binding site. For example, replacing Lys322 of full length human IgG with an Ala residue can ablate or eliminate the complement Clq binding site. In some aspects, replacing one or more of Glu318, Lys320, and Lys322 of full length mouse IgG with an Ala residue can ablate or eliminate the complement Clq binding site. In some aspects, ablating Clq binding to the disclosed monomeric Fc fragments comprises mutation position 107 of a monomeric Fc fragment of an immunoglobulin recognized by a FcRn. For example, a mutation of lysine to alanine shown at position 107 of SEQ ID NO:7 can ablate Clq binding to a human monomeric Fc fragment of an immunoglobulin recognized by a FcRn.

[0062] In some aspects, the FcRn binding sites are known to be His310 and His433 or His310/Gln311 (HQ) and His433/Asn434 (HN) of full length wild type IgG. The region of the Fc-fragment of IgG that binds to the FcRn receptor in humans has been described based upon X- ray crystallography (Burmaister, W. P. et al., Nature, 1994; 372:379-378; incorporated by reference in its entirety herein). The major contact area of Fc with the FcRn receptor is near the junction of the CH2 and CH3 domains. Potential contacts are residues 248, 250-257, 272, 285, 288, 290-291, 308-311 and 314 in CH2 and 385-387, 428 and 433-436 in CH3. In some aspects, no mutations would be present in the FcRn binding sites. Given the foregoing information, those of ordinary skill in the art will readily recognize that the monomeric Fc fragment of IgG can be modified according to well-recognized procedures such as site-directed mutagenesis and the like to yield modified monomeric Fc fragments or portions thereof that will be bound by the FcRn receptor. Such modifications include modifications remote from the FcRn contact sites as well as modifications within the contact sites that preserve or even enhance binding.

[0063] In some aspects, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn can be derived from any isotype that binds FcRn. The Fc-fragment should be chosen from an immunoglobulin known to bind the FcRn in the mucosa of the subject receiving the antigen- Fc vaccine. Immunoglobulin subclasses recognized by FcRn in different epithelial mucosa of animal subjects are known to a person in the art and can be found in Ober, R. J. et al, 2001, Int. Immunol. 13, 1551-9, incorporated by reference in its entirety herein. In some aspects, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn is derived from a mammalian immunoglobulin. For example, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn can be a human immunoglobulin sequence.

[0064] In some aspects, the amino acid sequence of a monomeric Fc fragment of a human IgGl can be

EPKSCDKTHTsPPsPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE VKFN WYVDGVEVHNAKTKPREEQYN STYRVV SVLTVLHQDWLNGKEYKCaV SNKALPAPIE KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 7) or a variant thereof. In some aspects, the variant can a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:7. The two cysteine to serine mutations are shown at positions 11 and 14. A lysine to alanine mutation is shown at position 107. The cysteine mutations allow for the Fc fragment to remain monomeric and not dimerize with another Fc fragment. The lysine to alanine mutation ablates Clq binding to the Fc fragment.

[0065] In some aspects, the amino acid sequence of a monomeric Fc fragment of a mouse IgG2a can be

EPRGPTIKPSPPSKSPAPNLLGGPSVFIFPPKIKDVLMISLSPIVTCVVVDVSEDDP DVQIS WFVNNVEVHTAQTQTHREDYNSTLRVVSALPIQHQDWMSGKAFACAVNNKDLPAPIE RTISKPKGSVRAPQVYVLPPPEEEMTKKQVTLTCMVTDFMPEDIYVEWTNNGKTELNY KNTEPVLDSDGSYFMYSKLRVEKKNWVERNSYSCSVVHEGLHNHHTTKSFSRTPGK (SEQ ID NO:E) or a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of (SEQ ID NO:E). The bold underlined amino acids represent a mutation from cysteine to serine to generate a single chain Fc.

[0066] In some aspects, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn comprises a full length Fc region of an immunoglobulin. In some aspects, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn comprises at least the CH2 and CH3 domains of a Fc region of an immunoglobulin. For example, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn comprises one or more of a full length CH2 and CH3 domain of IgG. In some aspects, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn comprises at least a portion of the one or more CH2 and CH3 domains so long as the portions of the one or more CH2 and CH3 domains retains the ability to be recognized by FcRn. [0067] In some instances, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn is conjugated to the amino or carboxy terminal end of SARS-CoV-2 antigen. For example, the SARS-CoV-2 antigen can be the spike protein or a fragment thereof. In some instances, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn is conjugated to the amino or carboxy terminal end of a trimerization domain. For example, the trimerization domain can be foldon. The conjugation can be direct or indirect. Indirect conjugation can be due to the presence of a linker in between the SARS-CoV-2 antigen or trimerization domain and the monomeric Fc fragment of an immunoglobulin recognized by a FcRn. Indirect conjugation can be due to the presence of another peptide in between the SARS- CoV-2 antigen or trimerization domain and the monomeric Fc fragment of an immunoglobulin recognized by a FcRn. [0068] In some aspects, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn can be derived from IgG. In some aspects, the IgG can be any IgG subtype. For example, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn can be derived from IgGl, IgG2, IgG3, or IgG4. ii. Trimerization Domain

[0069] The disclosed peptides have a trimerization domain.

[0070] The SARS-COV-2 S protein naturally exists as a trimer. Thus, disclosed herein are trimerization domains that allow the disclosed peptides, comprising one or more of the SARS- COV-2 S proteins, to trimerize. For example, three of the disclosed peptides can trimerize to form a peptide complex as disclosed herein.

[0071] In some instances, the trimerization domain is a T4 bacteriophage fibritin trimerization domain. For example, the T4 bacteriophage fibritin trimerization domain can be foldon which is present at the C-terminus of T4 bacteriophage fibritin. In some instances, the wild type amino acid sequence of foldon is GYIPEAPRDGQAYVRKDGEWVLLSTFL. In some instances, the amino acid sequence of foldon is 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the wild type foldon sequence. In some aspects, the nucleic acid sequence of foldon can be represented by the sequence

GGCTACATCCCCGAGGCCCCCAGAGACGGCCAGGCCTACGTGAGAAAGGACGGCG

AGTGGGTGCTGCTGAGCACCTTCCTG.

[0072] In some instances, the trimerization domain can be, but is not limited to the transcription factor GCN4pII trimerization motif

(MKQIEDKIEEILSKIYHIENEIARIKKLIGEV), or human collagen XV trimerization domain. In some instances, the trimerization domain can be an amino acid sequence that is 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to transcription factor GCN4pII trimerization motif or human collagen XV trimerization domain.

[0073] In some aspects, the trimerization domain is between the monomeric Fc fragment recognized by FcRn and the SARS-CoV-2 antigen. In some aspects, the trimerization domain is on the C-terminal end of the SARS-CoV-2 S protein. In some aspects, the trimerization domain is on the N-terminal end of the monomeric Fc fragment recognized by FcRn. iii. Coronavirus Antigen

[0074] In some aspects, the disclosed peptides can comprise a monomeric Fc fragment recognized by FcRn, a trimerization domain, and a coronavirus antigen. In some aspects, a coronavirus antigen can be any region of a coronavirus that can generate an immune response. In some aspects, a coronavirus antigen can be all or a portion of the coronavirus spike (S) protein. In some aspects, the coronavirus S protein is the soluble portion of the coronavirus S protein.

For example, the transmembrane domain and cytoplasmic domain are not present in the soluble portion of the coronavirus S protein. In some aspects, the coronavirus is Middle East respiratory syndrome coronavirus (MERS-CoV), Human Coronavirus — Erasmus Medical Centre (HCoV- EMC), SARS-CoV, or SARS-CoV-2. Thus, in some aspects, the coronavirus spike protein can be a MERS-CoV, HCoV-EMC, SARS-CoV, or SARS-CoV-2 spike protein, or antigenic fragment thereof.

[0075] In some aspects, the disclosed peptides can comprise a monomeric Fc fragment recognized by FcRn, a trimerization domain, and a SARS-COV-2 antigen. In some aspects, a SARS-COV-2 antigen can be any region of SARS-COV-2 that can generate an immune response. In some aspects, a SARS-COV-2 antigen can be all or a portion of the SARS-COV-2 S protein. In some aspects, the SARS-COV-2 S protein is the soluble portion of the SARS- COV-2 S protein. For example, the transmembrane domain and cytoplasmic domain are not present in the soluble portion of the SARS-COV-2 S protein.

[0076] In some aspects, a SARS-CoV-2 S protein can be derived from wild type SARS- CoV -2 or from a variant strain, such as, but not limited to, the variants of D614G (originally found in China/Germany), B.l.1.7 or 201/501 Y.V1 (originally found in the United Kingdom),

B.1.351 or 2QH/501.V2 (originally found in South Africa), P.l or 20J/501Y.V3 (originally found in Japan/Brazil), 20C/S:452R (originally found in California), and Cluster 5 Variant (originally found in Denmark).

[0077] In some aspects, the soluble portion of the SARS-COV-2 S protein is amino acids 1- 1213 of the full length wild type S protein. Specifically, the soluble portion of the SARS-COV - 2 S protein comprises the sequence

MFVFLVLLPLVSSOCVNLTTRTOLPPAYTNSFTRGVYYPDKVFRSSVLHSTODLFLP FFS

NVTWFH AIHV S GTN GTKRFDNP VLPFNDGV YF ASTEKSNIIRGWIF GTTLD S KT Q S LLIV

NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLM D

LEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINI TRFQ

TLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPL S

ETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPINITINLCPFGEVFNATRFASVYA WNR

KRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAP

CQTGKIADYNYKLPDDFTCCVIAWNSNNLDSKVGCNYNYLYRLFRKSNLKPFERD

ISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPAT

VCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQ

TLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYS TGS NVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRA4SVASQSIIAYTMSLG AENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFC T QLNRALT GI AVEQDKNT QEVF AQ VKQI YKTPPIKDFGGFNF SQILPDPS KP SKA£FIEDLL FNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTI TSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSST ASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLD¾EAEVQIDRLITGRL QSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHG VVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTD NTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVN IQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWP (SEQ ID NO: 8) or a variant thereof. In some aspects, the variant can be a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 8. The underlined sequence represents a native signal peptide of S protein. The bold shaded sequence represents the RBD of SI. The bold underline sequence represents the mutated S1/S2 cleavage site (R685A in italics, no change in S686). The bold letter and bold underline sequence represents a mutation at the S2’ cleavage site (R816A in italics, no change in S817). The bold, italics, and shaded sequence represents K986P and V987P mutations which allow the S protein to keep the Pre-fusion conformation.

[0078] In some aspects, the SARS-COV-2 S protein is the soluble portion of the D614G variant S protein. Specifically, the S protein of the D614G variant can comprise the sequence

MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLP FFS

NVTWFH AIHV S GTN GTKRFDNP VLPFNDGV YF ASTEKSNIIRGWIF GTTLD S KT Q S LLIV

NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLM D

LEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINI TRFQ

TLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPL S

ETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWN RKRI

SNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQT GK

IADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQ AG

STPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNL V

KNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCS FGG

VSVITPGTNTSNQVAVLYQgVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLI GA

EHVNN S YECDIPIGAGIC AS Y QTQTN S PRRARS V AS Q S II AYTM SLGAEN S V AY SNN S I AI

PTNFTISVTTEILPV SMTKTSVDCTMYICGDSTECSNLLLQY GSFCTQLNRALTGIAVEQD

KNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAG FIKQ YGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQ IPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQ NAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIR AAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQE KNFTTAPAICHDGKAHFPREGVFV SNGTHWFVTQRNFYEPQIITTDNTFV SGNCDVVIGI VNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAK NLNESLIDLOELGKYEOYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSC GSCCKFDEDDSEPVLKGVKLHYT (SEQ ID NO: 11) (with the mutation of D614G shown in lowercase) or a variant thereof. In some aspects, the variant can be a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 11. Amino acids 1-1213 of SEQ ID NO: 11 represent the soluble portion of the protein. Thus, amino acids 1214-1273 (shown here in underline) represent the transmembrane and cytoplasmic tail of SEQ ID NO: 11.

[0079] In some aspects, the SARS-COV-2 S protein is the soluble portion of the B.1.1.7 variant S protein. In some aspects, the B.1.1.7 variant S protein comprises deletions at amino acids 69, 70, and 144 and the following substitutions: N501Y, A570D, D614G, P681H, 17161.

S982A, DT118H (numbers are based on position prior to the deletion of amino acids 69, 70, and

144). Specifically, the S protein of the B.1.1.7 variant can comprise the sequence

MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLP FFS

NVTWFH AI S GTN GTKRFDNP VLPFND GVYF ASTEKSNIIRGWIF GTTLD SKT Q SLLI VNN

ATNVVIKVCEFQFCNDPFLGVYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLE G

KQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRF QTLL

ALHRS YLTPGD S S SGWTAGAAAYYVGYLQPRTFLLKYNENGTITD AVDC ALDPLSETK

CTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKR ISNC

VADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKI AD

YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGS TP

CNGVEGFNCYFPLQSYGFQPTYGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKN K

CVNFNFNGLTGTGVLTESNKKFLPFQQFGRDI IDTTDAVRDPQTLEILDITPCSFGGVSVI

TPGTNTSNQVAVLYQgVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEH V

NNSYECDIPIGAGICASYQTQTNShRRARSVASQSIIAYTMSLGAENSVAYSNNSIA IPINF

TISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQD KNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIK QYGD

CLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQI PFA

MQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNA Q ALNTLVKQLSSNFGAISSVLNDILARLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAE I RASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNF TTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTIINTFVSGNCDVVIGIVN N TVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNE SLIDLOELGKYEOYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC KFDEDDSEPVLKGVKLHYT (SEQ ID NO: 12) (substitutions shown in lowercase) or a variant thereof. In some aspects, the variant can be a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 12. Amino acids 1-1210 of SEQ ID NO: 12 represent the soluble portion of the protein. Thus, amino acids 1211-1270 (shown here in underline) represent the transmembrane and cytoplasmic tail of SEQ ID NO: 12. [0080] In some aspects, the SARS-COV-2 S protein is the soluble portion of the B.1.351 variant S protein. In some aspects, the B.1.351 variant S protein comprises the following substitutions D80A, D215G, K417N, A701V, N501Y, E484K. Specifically, the S protein of the B.1.351 variant can comprise the sequence

MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLP FFS

NVTWFH AIHV S GTN GTKRF aNP VLPFNDGV YF ASTEKSNIIRGWIF GTTLD SKT Q S LLIV

NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLM D

LEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRgLPQGFSALEPLVDLPIGINI TRFQT

LLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLS E

TKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNR KRIS

NCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTG nlA

DYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAG ST

PCNGVkGFNCYFPLQSYGFQPTvGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVK NK

CVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGG VSVI

TPGTNTSNQVAVLYQdVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEH V

NNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGvENSVAYSNNSIA IPTNF

TISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQD KNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIK QYGD

CLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQI PFA

MQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNA Q

ALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIR AAEI

RASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNF

TTAPAICHDGKAHFPREGVFV SNGTHWFVTQRNFYEPQIITTDNTFV SGNCDVVIGIVNN

TVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKN LNE SLIDLOELGKYEOYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC KFDEDDSEPVLKGVKLHYT (SEQ ID NO: 13) (substitutions shown in lowercase) or a variant thereof. In some aspects, the variant can be a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 13. Amino acids 1-1213 of SEQ ID NO: 13 represent the soluble portion of the protein. Thus, amino acids 1214-1273 (shown here in underline) represent the transmembrane and cytoplasmic tail of SEQ ID NO: 13. [0081] In some aspects, the SARS-COV-2 S protein is the soluble portion of the P.l variant S protein. In some aspects, the P.l variant S protein comprises the following substitutions L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, H655Y, T1027I. Specifically, the S protein of the P.l variant can comprise the sequence

MFVFLVLLPLVSSQCVNiT· RTQLPNAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSN

VTWFH AIH V S GTN GTKRFDNP VLPFNDGV YF AS TEKSNIIRGWIF GTTLD SKT Q SLLI VN

NATNVVIKVCEFQFCNvPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMD L

EGKQGNFKNLiEFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINIT RFQTL

LALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSE T

KCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRK RISN

CVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGt IAD

YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGS TP

CNGVkGFNCYFPLQSYGFQPTvGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKN K

CVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGG VSVI

TPGTNTSNQVAVLYQdVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEv VN

NSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAI PTNFT

ISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDK NTQ

EVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQ YGDC

LGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIP FAM

QMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQ A

LNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRA AEIR

ASANLAAsKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFT T

AP AICHDGKAHFPREGVF V SN GTHWF VT QRNF YEP QIITTDNTFV S GN CD VVIGI VNNT

VYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNL NES

LIDLOELGKYEOYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSC CK

FDEDDSEPVLKGVKLHYT (SEQ ID NO: 14) (substitutions shown in lowercase) or a variant thereof. In some aspects, the variant can be a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%,

95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 14. Amino acids 1-1213 of SEQ ID NO: 14 represent the soluble portion of the protein. Thus, amino acids 1214-1273 (shown here in underline) represent the transmembrane and cytoplasmic tail of SEQ ID NO: 14. [0082] In some aspects, the SARS-COV-2 S protein is the soluble portion of the 20C/S:452R variant S protein. In some aspects, the 20C/S:452R variant S protein comprises the following substitutions S 131, W152C, L452R. Specifically, the S protein of the 20C/S:452R variant can comprise the sequence

MFVFLVLLPLVS;QCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLP FFS

NVTWFH AIHV S GTN GTKRFDNP VLPFNDGV YF ASTEKSNIIRGWIF GTTLD S KT Q S LLIV

NNATNVVIKVCEFQFCNDPFLGVYYHKNNKScMESEFRVYSSANNCTFEYVSQPFLM D

LEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINI TRFQ

TLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPL S

ETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWN RKRI

SNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQT GK

IADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYrYRLFRKSNLKPFERDISTEIYQ AG

STPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNL V

KNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCS FGG

VSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLI GA

EHVNN S YECDIPIGAGIC AS Y QTQTN S PRRARS V AS Q S II AYTM SLGAEN S V AY SNN S I AI

PTNFTISVTTEILPV SMTKTSVDCTMYICGDSTECSNLLLQY GSFCTQLNRALTGIAVEQD

KNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAG FIKQ

YGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAA LQ

IPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVV NQ

NAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQ LIR

AAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQ E

KNFTTAPAICHDGKAHFPREGVFV SNGTHWFVTQRNFYEPQIITTDNTFV SGNCDVVIGI

VNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEV AK

NLNESLIDLOELGKYEOYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCC SC

GSCCKFDEDDSEPVLKGVKLHYT (SEQ ID NO: 15) (substitutions shown in lowercase) or a variant thereof. In some aspects, the variant can be a sequence 50%, 55%, 65%, 70%, 75%,

80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 15. Amino acids 1-1213 of SEQ ID NO: 15 represent the soluble portion of the protein. Thus, amino acids 1214-1273 (shown here in underline) represent the transmembrane and cytoplasmic tail of SEQ ID NO:15.

[0083] In some aspects, the SARS-COV-2 S protein is the soluble portion of the cluster 5 variant S protein. In some aspects, the cluster 5 variant S protein comprises deletions at amino acids 69, 70 and the following substitutions U453F, I692V, and Ml 2291. Specifically, the S protein of the cluster 5 variant can comprise the sequence

MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLP FFS

NVTWFH AI S GTN GTKRFDNP VLPFND GVYF ASTEKSNIIRGWIF GTTLD SKT Q SLLI VNN

ATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDL E

GKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR FQTL

LALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSE T

KCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRK RISN

CVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGK IA

DYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLfRLFRKSNLKPFERDISTEIYQAG ST

PCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVK N

KCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFG GVS

VITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGA E

HVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSE AYTMSLGAENSVAYSNNSIAIP

TNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAV EQD

KNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAG FIKQ

YGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAA LQ

IPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVV NQ

NAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQ LIR

AAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQ E

KNFTTAPAICHDGKAHFPREGVFV SNGTHWFVTQRNFYEPQIITTDNTFV SGNCDVVIGI

VNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEV AK

NLNESLIDLOELGKYEOYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCC SC

GSCCKFDEDDSEPVLKGVKLHYT (SEP ID NO: 161 (substitutions shown in lowercase) or a variant thereof. In some aspects, the variant can be a sequence 50%, 55%, 65%, 70%, 75%,

80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 16. Amino acids 1-1210 of SEQ ID NO: 16 represent the soluble portion of the protein. Thus, amino acids 1214-1270 (shown here in underline) represent the transmembrane and cytoplasmic tail of SEQ ID NO: 16.

[0084] In some aspects, the SARS-COV-2 S protein can be cleaved into SI and S2 subunits by proteases. In some aspects, SI comprises the receptor-binding domain (RBD) which allows viruses to directly bind to the ACE2 receptor. In some aspects, S2 can mediate membrane fusion, with the help of a protease, in cells. In some aspects, the SARS-COV-2 S protein (“S protein”) is the full length soluble S protein, the SI subunit, the S2 subunit, or the RBD. In some aspects, the SARS-COV-2 S protein is a portion of full length soluble S protein, the SI subunit, the S2 subunit, or the RBD. In some aspects, the SARS-COV-2 S protein is a variant of a wild type sequence and thus, is 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, 99, or 100% identical to the wild type full length S protein, the SI subunit, the S2 subunit, or the RBD. In some aspects, a variant SARS-COV-2 S protein can comprise a modified amino acid or a non- naturally occurring amino acid.

[0085] In some aspects, the complete wild type amino acid sequence of SARS-COV-2 can be found in Genbank as accession number MN908947. The S protein is nucleic acids 21563- 25384 of accession number MN908947.

[0086] In some aspects, the S protein is the full length S protein. Because the S protein can be cleaved by proteases, in some aspects, the disclosed SARS-COV-2 S protein can be altered or mutated to remove the cleavage sites and produce a non-cleavable S protein. In some aspects, the mutations that remove the cleavage site are R685A and R816A of the full length wild type S protein. For example, the cleavage sites of R685A and R816A are at positions 685 and 816, respectively, of SEQ ID NO: 8.

[0087] In some aspects, the S protein can be further altered or mutated so that the S protein retains its prefusion state. In some aspects, mutations that maintain the S protein in a prefusion state can be K986P and V987P. iv. Linkers

[0088] Disclosed are peptides comprising a monomeric Fc fragment of an immunoglobulin recognized by FcRn; a SARS-CoV-2 antigen; and a trimerization domain, wherein the peptide further comprises one or more linkers.

[0089] In some instances, at least one of the one or more linkers is on the N-terminus end of the monomeric Fc fragment of an immunoglobulin recognized by a FcRn. In some instances, at least one of the one or more linkers is on the C-terminus end of the monomeric Fc fragment of an immunoglobulin recognized by a FcRn.

[0090] In some instances, at least one of the one or more linkers is located between the SARS-CoV-2 antigen and the monomeric Fc fragment of an immunoglobulin recognized by a FcRn. In some instances, at least one of the one or more linkers is located between the trimerization domain and the monomeric Fc fragment of an immunoglobulin recognized by a FcRn. In some instances, at least one of the one or more linkers is located between the trimerization domain and the SARS-CoV-2 antigen.

[0091] In some instances, the one or more linkers are small, nonpolar, amino acid linkers. For example, the linker can be a GS-linker. The number of glycine, serine, and glycine/serine repeats can vary in the one or more linkers. Examples of GS linkers can be GSGSGS and GSGGGGSGGGGSGS. v. Additional elements

[0092] In some aspects, the disclosed peptides comprise a signal peptide. In some aspects, a signal peptide is any short peptide (about 10-30 amino acids) that help translocate the peptide to the cell membrane. In some aspects, the signal peptide is present on the N-terminal end of the SARS-CoV-2 antigen. In some aspects, the signal peptide is derived from the coronavirus antigen. In some aspects, the signal peptide is derived from the SARS-CoV-2 antigen. For example, the native signal peptide found on SARS-CoV-2 S protein can be present in the disclosed peptides. In some aspects, the native signal peptide can comprise the amino acid sequence of MFVFLVLLPLVSSQC from SARS-CoV-2 S protein. In some aspects, a signal peptide can comprise one or more of the sequences present in Table 1.

Table 1. Exemplary signal peptide sequences.

[0093] In some instances, the disclosed peptides can further comprise cleavage sites or tag sequences.

[0094] In some instances, a cleavage site can be present in the disclosed peptides. Cleavage sites can allow for cleavage of the monomeric Fc fragment of an immunoglobulin recognized by FcRn away from the SARS-CoV-2 antigen. In some instances, a cleavage site can be recognized by a protease or a chemical compound. In some instances, a cleavage site can be a site recognized by, but not limited to, enterokinase, pepsin, factor Xa, tobacco etch virus protease, or thrombin.

[0095] In some instances, a tag sequence can be present in the disclosed peptides. In some instances, a tag sequence can be a detection label/label sequence or a purification tag. As used herein, a detection label or label sequence is any molecule that can be associated with a nucleic acid or peptide, directly or indirectly, and which results in a measurable, detectable signal, either directly or indirectly. Many such labels for incorporation into nucleic acids or coupling to nucleic acids or peptides are known to those of skill in the art. Examples of detection labels can be, but are not limited to, radioactive isotopes, fluorescent molecules, phosphorescent molecules, enzymes, antibodies, and ligands.

[0096] Examples of suitable fluorescent labels include fluorescein (FITC), 5,6- carboxymethyl fluorescein, Texas red, nitrobenz-2-oxa-l,3-diazol-4-yl (NBD), coumarin, dansyl chloride, rhodamine, 4'-6-diamidino-2-phenylinodole (DAPI), and the cyanine dyes Cy3, Cy3.5, Cy5, Cy5.5 and Cy7. Preferred fluorescent labels are fluorescein (5-carboxyfluorescein-N- hydroxysuccinimide ester) and rhodamine (5,6-tetramethyl rhodamine). Preferred fluorescent labels for combinatorial multicolor coding are FITC and the cyanine dyes Cy3, Cy3.5, Cy5, Cy5.5 and Cy7. The absorption and emission maxima, respectively, for these fluors are: FITC (490 nm; 520 nm), Cy3 (554 nm; 568 nm), Cy3.5 (581 nm; 588 nm), Cy5 (652 nm: 672 nm), Cy5.5 (682 nm; 703 nm) and Cy7 (755 nm; 778 nm), thus allowing their simultaneous detection. The fluorescent labels can be obtained from a variety of commercial sources, including Molecular Probes, Eugene, OR and Research Organics, Cleveland, Ohio.

[0097] In some instances, a label sequence can be, but is not limited to, an isotope marker, colorimetric biosensors, or fluorescent labels. For example, fluorescent markers can be, but are not limited to, green fluorescent protein (GFP) or rhodamine fluorescent protein (RFP). Other label sequences can include biotin, streptavidin, horseradish peroxidase, or luciferase.

[0098] In some instances, a tag sequence can be a purification tag. In some instances, a purification tag can be, but is not limited to, histidine, glutathione-S-transferase, albuminbinding protein, FLAG epitope, galactose-binding protein, myc, or hemagglutinin.

[0099] In some aspects, the compositions or peptides disclosed herein can further comprise an adjuvant. In some aspects, the adjuvant is immunostimulatory oligonucleotides containing unmethylated CpG dinucleotides (“CpG”). CpGs are known in the art as being adjuvants when administered by both systemic and mucosal routes (WO 96/02555, EP 468520, Davis et al., J. Immunol, 1998, 160(2): 870-876, McCluskie and Davis, J. Immunol., 1998, 161(9): 4463-6). CpG is an abbreviation for cytosineguanosinc dinucicotide motifs present in DNA. Historically, it was observed that the DNA fraction of BCG could exert an anti -tumour effect. In further studies, synthetic oligonucleotides derived from BCG gene sequences were shown to be capable of inducing immunostimulatory effects (both in vitro and in vivo). The authors of these studies concluded that certain palindromic sequences, including a central CG motif, carried this activity. The central role of the CG motif in immunostimulation was later elucidated in a publication by Krieg, 1995, Nature 374, p. 546. Detailed analysis has shown that the CG motif has to be in a certain sequence context, and that such sequences are common in bacterial DNA but are rare in vertebrate DNA. The immunostimulatory sequence is often: Purine, Purine, C, G, pyrimidine, pyrimidine; wherein the dinucleotide CG motif is not methylated, but other unmethylated CpG sequences are known to be immunostimulatory and may be used in the present invention, vi. Example peptides

[00100] Disclosed are peptides comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS-CoV-2 soluble S protein; and a trimerization domain. For example, disclosed are peptides comprising the amino acid sequence of

MFVFLVLLPLVSSOCVNLTTRTOLPPAYTNSFTRGVYYPDKVFRSSVLHSTODLFLP FFS

NVTWFH AIHV S GTN GTKRFDNP VLPFNDGV YF ASTEKSNIIRGWIF GTTLD S KT Q S LLIV

NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLM D

LEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINI TRFQ

TLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPL S

ETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPMTNLCPFGEVFNATRFASVYAWNR

KRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAP

GQTGK1ADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERD

ISTEIYQAGSTPCNGVEGFINCYFPLQSYC FQPTNGVGYQPYRVVVLSFELLHAPAT

VCCPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQ

TLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYS TGS

NVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRAASVASQSIIAYTM SLG

AENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYG SFCT

QLNRALT GI AVEQDKNT QEVF AQ VKQI YKTPPIKDFGGFNF SQILPDPS KP SKA£FIEDLL

FNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLA GTI TSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSST

ASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLD££EAEVQIDRL ITGRL

QSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPH G

VVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIIT TD

NTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINAS VVN

IOKEIDRLNEVAKNLNESLIDLOELGKYEOYIKWPGSGSGSRSLVPRGSPGSGYIPE APRD

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCflVSNKALPAPIEKTISKAKGQPREPQVYTL PPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 1) or a variant thereof. In some aspects, the variant can a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:l. The underlined sequence represents a native signal peptide of S protein. The bold shaded sequence represents the RBD of SI. The bold underline sequence represents the mutated S1/S2 cleavage site (R685A of S protein in italics, no change in S686 of S protein). The bold letter and bold underline sequence represents a mutation at the S2’ cleavage site (R816A of S protein in italics, no change in S817 of S protein). The bold, italics, and shaded sequence represents K986P and V987P mutations (of the S protein) which allow the S protein to keep the Pre-fusion conformation. The dotted underline and shaded sequence represents a 6GS (glycine-serine) linker. The double squiggle underline represents the foldon domain from T4 fibrin. The dotted underline, italicized shaded sequence represents a 14GS (glycine-serine) linker. The bold sequence is human IgGl. The dotted underline lowercase sequence S represents a cysteine to serine mutation (C226S of human IgGl, Ser at position 1283 of SEQ ID NO: 1) in human IgGl to produce a monomer human IgGl. The dotted underline lowercase sequence S represents a cysteine to serine mutation (C229S of human IgGl, Ser at position 1286 of SEQ ID NO: 1) in human IgGl to produce a monomer human IgGl. The italicized, underlined lowercase sequence represents a mutation preventing complement binding (K322A of human IgGl, Ala at position 1379 of SEQ ID NO: 1) in human IgGl. Amino acids 16 to 1213 represent the SARS- Cov-2 spike protein. Amino acids 1229 to 1257 represent the foldon domain of T4 fibrin.

Amino acids 1273 to 1504 represent a monomeric Fc IgGl fragment.

[00101] Disclosed are peptides comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS-CoV-2 SI protein; and a trimerization domain. For example, disclosed are peptides comprising the amino acid sequence of MFVFLVLLPLVSSOCVNLTTRTOLPPAYTNSFTRGVYYPDKVFRSSVLHSTODLFLPFFS NVTWFH AIHV S GTN GTKRFDNP VLPFNDGV YF ASTEKSNIIRGWIF GTTLD S KT Q S LLIV NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMD LEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRF Q TLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLS ETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPMTNLCPFGEVFNATRFASVYAWNR KRISINCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAP GQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERD ISTEIYQAGSTPCNGVEGFIMCYFPLQSYGFQPTNGVGYQPYRVWLSFELLHAPAT VCCPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQ TLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGS NVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRAAGSGSGSRSLVPRGSP GSGYIPEAPRDGOAYVRKDGEWVLLSTFLGGriGY/GYkSYif /GYkSYkSEPKSCDKTFITsPPsPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYN STYRVV SVLTVLHQDWLNGKEYKCaV SNKALP APIEKTISKAKGQPREPQV YTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:3) or a variant thereof. In some aspects, the variant can a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 3. The underlined sequence represents a native signal peptide of S protein. The bold shaded sequence represents the RBD of SI. The bold underline sequence represents the mutated S1/S2 cleavage site (R685A in italics). The dotted underline and shaded sequence represents a 6GS (glycine-serine) linker. The double squiggle underline represents the foldon domain from T4 fibrin. The dotted underline, italicized shaded sequence represents a 14GS (glycine-serine) linker. The bold sequence is human IgGl. The dotted underline lowercase sequence S represents a cysteine to serine mutation (C226S of human IgGl, Ser at position 755 of SEQ ID NO:3) in human IgGl to produce a monomer human IgGl. The dotted underline lowercase sequence S represents a cysteine to serine mutation (C229S of human IgGl, Ser at position 758 of SEQ ID NO:3) in human IgGl to produce a monomer human IgGl. The italicized, underlined lowercase sequence represents a mutation preventing complement binding (K322A of human IgGl, Ala at position 851 of SEQ ID NO:3) in human IgGl. Amino acids 16 to 685 represent the SARS- Cov-2 SI protein. Amino acids 701 to 729 represent the foldon domain of T4 fibrin. Amino acids 745 to 976 represent a monomeric Fc IgGl fragment.

[00102] Disclosed are peptides comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS-CoV-2 RBD protein; and a trimerization domain. For example, disclosed are peptides comprising the amino acid sequence of

MFVFLVLLPLVSSOCVRVOPTESIVRFP1MT1NLCPFGEVF1NATRFASVYAWNRKR 1S1N

CVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTG

KIADYINYKLPDDFTCCVIAWNSNNLDSKVCGNYNYLYRLFRKSNLKPFERDISTEI

YQAGSTPCNGVEGFNCYFPLQSYGFQPTIMGVGYQPYRVVVLSFELLHAPATVCGP

KKSTNLVKNKCVNFGSGSGSRSLVPRGSPGSGYIPEAPRDGOAYVRKDGEWVLLSTF L

G G SG GG G SG GG G SG SEPKSC D K I H I sPPsPAPFEEGGPS\ FEFPPKPKI) I EMISR I PF

VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCflVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS CSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 5) or a variant thereof. In some aspects, the variant can a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 5. The underlined sequence represents a native signal peptide of S protein. The bold shaded sequence represents the RBD of SI. The dotted underline and shaded sequence represents a 6GS (glycine-serine) linker. The double squiggle underline represents the foldon domain from T4 fibrin. The dotted underline, italicized shaded sequence represents a 14GS (glycine-serine) linker. The bold sequence is human IgGl. The dotted underline lowercase sequence S represents a cysteine to serine mutation (C226S of human IgGl, Ser at position 309 of SEQ ID NO:5) in human IgGl to produce a monomer human IgGl. The dotted underline lowercase sequence S represents a cysteine to serine mutation (C229S of human IgGl, Ser at position 312 of SEQ ID NO:5) in human IgGl to produce a monomer human IgGl. The italicized, underlined lowercase sequence represents a mutation preventing complement binding (K322A of human IgGl, Ala at position 405 of SEQ ID NO:5) in human IgGl. Amino acids 17 to 239 represent the SARS-Cov-2 RBD protein. Amino acids 255 to 283 represent the foldon domain of T4 fibrin. Amino acids 299 to 530 represent a monomeric Fc IgGl fragment.

2. Peptides without a trimerization domain

[00103] Disclosed are peptides comprising a Fc fragment of an immunoglobulin recognized by a FcRn and a coronavirus antigen. In some aspects, the coronavirus antigen can be any coronavirus spike protein, or antigenic fragment thereof. In some aspects, the coronavirus is Middle East respiratory syndrome coronavirus (MERS-CoV), Human Coronavirus — Erasmus Medical Centre (HCoV-EMC), SARS-CoV, or SARS-CoV-2. Thus, in some aspects, the coronavirus spike protein can be a MERS-CoV, HCoV-EMC, SARS-CoV, or SARS-CoV-2 spike protein, or antigenic fragment thereof. In some aspects, the peptides do not comprise a trimerization domain.

[00104] Disclosed are peptides comprising a Fc fragment of an immunoglobulin recognized by a FcRn and a SARS-CoV-2 antigen. In some aspects, the SARS-CoV-2 antigen can be a SARS-CoV-2 spike protein. Thus, disclosed are peptides comprising a Fc fragment of an immunoglobulin recognized by a FcRn and a SARS-CoV-2 spike protein. In some aspects, the peptides do not comprise a trimerization domain.

[00105] Disclosed are peptides comprising a Fc fragment of an immunoglobulin recognized by a FcRn and a SARS-CoV-2 RBD protein. Thus, disclosed are peptides comprising a Fc fragment of an immunoglobulin recognized by a FcRn and a SARS-CoV-2 RBD protein. [00106] In some instances, the Fc fragment of an immunoglobulin recognized by a FcRn is conjugated to the amino or carboxy terminal end of a coronavirus antigen. The conjugation can be direct or indirect. Indirect conjugation can be due to the presence of a linker, for example, a linker can be present in between the coronavirus antigen and the Fc fragment of an immunoglobulin recognized by a FcRn. In some aspects, the peptides do not comprise a trimerization domain.

[00107] Disclosed are peptides encoded by one or more of the nucleic acid sequences provided herein. i. Fc fragment

[00108] A Fc fragment of an immunoglobulin recognized by a FcRn, as disclosed herein, can be any Fc fragment that can be recognized by a FcRn and is capable of forming a dimeric structure. In some aspects, a Fc fragment of an immunoglobulin recognized by a FcRn can comprise only the Fc portion of an immunoglobulin.

[00109] In some aspects, unlike the monomeric Fc fragment of an immunoglobulin recognized by a FcRn, the Fc fragment of an immunoglobulin recognized by a FcRn capable of forming a dimeric structure retains the cysteine residues responsible for dimer formation in native IgG.

[00110] For example, positions 226 and 229 of the full length sequence of the wild type sequence of human IgGl are not mutated and thus retain the ability for dimer formation. In some aspects, positions 11 and 14 of a sequence comprising only the hinge region, CH2 and CH3 domains of wild type IgG are not mutated. For example, the cysteine residues at positions 11 and 14 of SEQ ID NO: 17 are not mutated. In some aspects, positions 11 and 14 of SEQ ID NO:7 are located in the hinge region of Fc fragments of an immunoglobulin recognized by a FcRn that retain the ability to form dimers. [00111] In some aspects, the Clq binding site can be ablated in the Fc fragment that retains the ability for dimer formation. This can be effective to help avoid clearance of the Fc fragments via the complement pathway and thus allowing the disclosed peptides comprising a Fc fragment and coronavirus antigen to remain in a subject and provide its therapeutic effect. In some aspects, Clq is known to bind to the CH2 domain of an immunoglobulin, particularly IgG. In some aspects, substituting the lysine at position 322 of wild type human IgG can ablate or eliminate the complement Clq binding site. For example, replacing Lys322 of full length human IgG with an Ala residue can ablate or eliminate the complement Clq binding site. In some aspects, replacing one or more of Glu318, Lys320, and Lys322 of full length mouse IgG with an Ala residue can ablate or eliminate the complement Clq binding site. In some aspects, ablating Clq binding to the disclosed monomeric Fc fragments comprises mutation position 107 of a Fc fragment of an immunoglobulin recognized by a FcRn that retains the ability for dimer formation. For example, a mutation of lysine to alanine shown at position 107 of SEQ ID NO: 17 can ablate Clq binding to a human Fc fragment of an immunoglobulin recognized by a FcRn.

[00112] In some aspects, the FcRn binding sites are known to be His310 and His433 or His310/Gln311 (HQ) and His433/Asn434 (HN) of full length wild type IgG. The region of the Fc-fragment of IgG that binds to the FcRn receptor in humans has been described based upon X- ray crystallography (Burmaister, W. P. et ak, Nature, 1994; 372:379-378; incorporated by reference in its entirety herein). The major contact area of Fc with the FcRn receptor is near the junction of the CH2 and CH3 domains. Potential contacts are residues 248, 250-257, 272, 285, 288, 290-291, 308-311 and 314 in CH2 and 385-387, 428 and 433-436 in CH3 of wild type IgG. In some aspects, no mutations would be present in the FcRn binding sites. Given the foregoing information, those of ordinary skill in the art will readily recognize that the monomeric Fc fragment of IgG can be modified according to well-recognized procedures such as site-directed mutagenesis and the like to yield modified monomeric Fc fragments or portions thereof that will be bound by the FcRn receptor. Such modifications include modifications remote from the FcRn contact sites as well as modifications within the contact sites that preserve or even enhance binding.

[00113] In some aspects, the Fc fragment of an immunoglobulin recognized by a FcRn that retains the ability for dimer formation can be derived from any isotype that binds FcRn. The Fc- fragment should be chosen from an immunoglobulin known to bind the FcRn in the mucosa of the subject receiving the antigen-Fc vaccine. Immunoglobulin subclasses recognized by FcRn in different epithelial mucosa of animal subjects are known to a person in the art and can be found in Ober, R. J. et al, 2001, Int. Immunol. 13, 1551-9, incorporated by reference in its entirety herein. In some aspects, the Fc fragment of an immunoglobulin recognized by a FcRn is derived from a mammalian immunoglobulin. For example, the Fc fragment of an immunoglobulin recognized by a FcRn can be a human immunoglobulin sequence.

[00114] In some aspects, the amino acid sequence of a Fc fragment of a human IgGl that retains the ability for dimer formation can be

EPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE VKF NWYVDGVEVHNAKTKPREEQYNSTYRVV SVLTVLHQDWLNGKEYKCaV SNKALPAPI EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 17) or a variant thereof. In some aspects, the variant can a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 17. The two cysteine residues at positions 11 and 14 help retain the ability for dimer formation. A lysine to alanine mutation is shown at position 107. The lysine to alanine mutation ablates Clq binding to the Fc fragment.

[00115] In some aspects, the amino acid sequence of a Fc fragment of an immunoglobulin recognized by a FcRn that retains the ability for dimer formation of a mouse IgG2a can be EPRGPTIKPCPPCKSPAPNLLGGPSVFIFPPKIKDVLMISLSPIVTCVVVDVSEDDPDVQ IS WFVNNVEVHTAQTQTHREDYNSTLRVVSALPIQHQDWMSGKAFACAVNNKDLPAPIE RTI SKPKGS VRAP Q V YVLPPPEEEMTKKQ VTLTCMVTDFMPEDI YVEWTNN GKTELNY KNTEPVLDSDGSYFMYSKLRVEKKNWVERNSYSCSVVHEGLHNHHTTKSFSRTPGK (SEQ ID NO: 18) or a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of (SEQ ID NO: 18).

[00116] In some aspects, the Fc fragment of an immunoglobulin recognized by a FcRn that retains the ability for dimer formation comprises a full length Fc region of an immunoglobulin. In some aspects, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn comprises at least the CH2 and CH3 domains of a Fc region of an immunoglobulin. For example, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn comprises one or more of a full length CH2 and CH3 domain of IgG. In some aspects, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn comprises at least a portion of the one or more CH2 and CH3 domains so long as the portions of the one or more CH2 and CH3 domains retains the ability to be recognized by FcRn.

[00117] In some aspects, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn is conjugated to the amino or carboxy terminal end of a SARS-CoV-2 antigen. For example, the SARS-CoV-2 antigen can be the spike protein or a fragment thereof, such as RBD. The conjugation can be direct or indirect. Indirect conjugation can be due to the presence of a linker in between the SARS-CoV-2 antigen and the Fc fragment of an immunoglobulin recognized by a FcRn. Indirect conjugation can be due to the presence of another peptide in between the SARS-CoV-2 antigen and the Fc fragment of an immunoglobulin recognized by a FcRn.

[00118] In some aspects, the Fc fragment of an immunoglobulin recognized by a FcRn that retains the ability for dimerization can be derived from IgG. In some aspects, the IgG can be any IgG subtype. For example, the monomeric Fc fragment of an immunoglobulin recognized by a FcRn can be derived from IgGl, IgG2, IgG3, or IgG4. ii. Coronavirus Antigen

[00119] In some aspects, the disclosed peptides can comprise a Fc fragment of an immunoglobulin recognized by a FcRn and a coronavirus antigen. In some aspects, a coronavirus antigen can be any region of a coronavirus that can generate an immune response. In some aspects, a coronavirus antigen can be all or a portion of the coronavirus spike (S) protein.

In some aspects, the coronavirus S protein is the soluble portion of the coronavirus S protein.

For example, the transmembrane domain and cytoplasmic domain are not present in the soluble portion of the coronavirus S protein. In some aspects, the coronavirus is Middle East respiratory syndrome coronavirus (MERS-CoV), Human Coronavirus — Erasmus Medical Centre (HCoV- EMC), SARS-CoV, or SARS-CoV-2. Thus, in some aspects, the coronavirus spike protein can be a MERS-CoV, HCoV-EMC, SARS-CoV, or SARS-CoV-2 spike protein, or antigenic fragment thereof.

[00120] In some aspects, the disclosed peptides can comprise a Fc fragment of an immunoglobulin recognized by a FcRn and a SARS-COV-2 antigen. In some aspects, a SARS- COV-2 antigen can be any region of SARS-COV-2 that can generate an immune response. In some aspects, a SARS-COV-2 antigen can be all or a portion of the SARS-COV-2 S protein. In some aspects, the SARS-COV-2 S protein is the soluble portion of the SARS-COV-2 S protein. For example, the transmembrane domain and cytoplasmic domain are not present in the soluble portion of the SARS-COV-2 S protein.

[00121] In some aspects, a SARS-CoV-2 S protein can be derived from wild type SARS- CoV -2 or from a variant strain, such as, but not limited to, the variants of D614G (originally found in China/Germany), B.l.1.7 or 20I/501Y.V1 (originally found in the United Kingdom),

B.1.351 or 20H/501.V2 (originally found in South Africa), P.l or 20J/501Y.V3 (originally found in Japan/Brazil), 20C/S:452R (originally found in California), and Cluster 5 Variant (originally found in Denmark).

[00122] In some aspects, the soluble portion of the SARS-COV-2 S protein is amino acids 1- 1213 of the full length wild type S protein. Specifically, the soluble portion of the SARS-COV- 2 S protein comprises the sequence

MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLP FFS

NVTWFH AIHV S GTN GTKRFDNP VLPFNDGV YF ASTEKSNIIRGWIF GTTLD S KT Q S LLIV

NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLM D

LEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINI TRFQ

TLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPL S

ETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWN R

KRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAP

GQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERD

ISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPAT

VCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQ

TLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYS TGS

NVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRAASVASQSIIAYTM SLG

AENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYG SFCT

QLNRALT GI AVEQDKNT QEVF AQ VKQI YKTPPIKDFGGFNF SQILPDPS KP SKASFIEDLL

FNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLA GTI

TSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLS ST

ASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLIT GRL

QSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPH G

VVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIIT TD

NTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINAS VVN

IQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWP (SEQ ID NO: 8) or a variant thereof. In some aspects, the variant can be a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%,

97%, 98%, or 99% identical to the sequence of SEQ ID NO: 8. The bold sequence represents the

RBD of SI.

[00123] In some aspects, the SARS-COV-2 S protein is the soluble portion of the D614G variant S protein. Specifically, the S protein of the D614G variant can comprise the sequence of SEQ ID NO: 11 (with the mutation of D614G shown in lowercase) or a variant thereof. In some aspects, the variant can be a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 11. In some aspects, the SARS-COV-2 S protein is the RBD portion of the D614G variant S protein. [00124] In some aspects, the SARS-COV-2 S protein is the soluble portion of the B.1.1.7 variant S protein. Specifically, the S protein of the B.l.1.7 variant can comprise the sequence of SEQ ID NO: 12 or a variant thereof. In some aspects, the variant can be a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:12. In some aspects, the SARS-COV-2 S protein is the RBD portion of the B.l.1.7 variant S protein.

[00125] In some aspects, the SARS-COV-2 S protein is the soluble portion of the B.1.351 variant S protein. Specifically, the S protein of the B.1.351 variant can comprise the sequence of SEQ ID NO: 13 or a variant thereof. In some aspects, the variant can be a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 13. In some aspects, the SARS-COV-2 S protein is the RBD portion of the B.1.351 variant S protein.

[00126] In some aspects, the SARS-COV-2 S protein is the soluble portion of the P.1 variant S protein. Specifically, the S protein of the P.1 variant can comprise the sequence of SEQ ID NO: 14 or a variant thereof. In some aspects, the variant can be a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 14. In some aspects, the SARS-COV-2 S protein is the RBD portion of the P.1 variant S protein.

[00127] In some aspects, the SARS-COV-2 S protein is the soluble portion of the 20C/S:452R variant S protein. Specifically, the S protein of the 20C/S:452R variant can comprise the sequence of SEQ ID NO: 15 or a variant thereof. In some aspects, the variant can be a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 15. In some aspects, the SARS-COV-2 S protein is the RBD portion of the 20C/S:452R variant S protein.

[00128] In some aspects, the SARS-COV-2 S protein is the soluble portion of the cluster 5 variant S protein. Specifically, the S protein of the cluster 5 variant can comprise the sequence of SEQ ID NO: 16 or a variant thereof. In some aspects, the variant can be a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 16. In some aspects, the SARS-COV-2 S protein is the RBD portion of the cluster 5 variant S protein.

[00129] In some aspects, the SARS-COV-2 S protein can be cleaved into SI and S2 subunits by proteases. In some aspects, SI comprises the receptor-binding domain (RBD) which allows viruses to directly bind to the ACE2 receptor. In some aspects, S2 can mediate membrane fusion, with the help of a protease, in cells. In some aspects, the SARS-COV-2 S protein (“S protein”) is the full length soluble S protein, the SI subunit, the S2 subunit, or the RBD. In some aspects, the SARS-COV-2 S protein is a portion of full length soluble S protein, the SI subunit, the S2 subunit, or the RBD. In some aspects, the SARS-COV-2 S protein is a variant of a wild type sequence and thus, is 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, 99, or 100% identical to the wild type full length S protein, the SI subunit, the S2 subunit, or the RBD. In some aspects, a variant SARS-COV-2 S protein can comprise a modified amino acid or a non- naturally occurring amino acid.

[00130] In some aspects, the complete wild type amino acid sequence of SARS-COV-2 can be found in Genbank as accession number MN908947. The S protein is nucleic acids 21563- 25384 of accession number MN908947.

[00131] In some aspects, the S protein is the full length S protein. Because the S protein can be cleaved by proteases, in some aspects, the disclosed SARS-COV-2 S protein can be altered or mutated to remove the cleavage sites and produce a non-cleavable S protein. In some aspects, the mutations that remove the cleavage site are R685A and R816A of the full length wild type S protein. For example, the cleavage sites of R685A and R816A are at positions 685 and 816, respectively, of SEQ ID NO: 8.

[00132] In some aspects, the S protein can be further altered or mutated so that the S protein retains its prefusion state. In some aspects, mutations that maintain the S protein in a prefusion state can be K986P and V987P. iii. Linkers

[00133] Disclosed are peptides comprising a Fc fragment of an immunoglobulin recognized by FcRn that retains the ability for dimer formation and a SARS-CoV-2 antigen, wherein the peptide further comprises one or more linkers.

[00134] In some instances, at least one of the one or more linkers is on the N-terminus end of the Fc fragment of an immunoglobulin recognized by a FcRn. In some instances, at least one of the one or more linkers is on the C-terminus end of the Fc fragment of an immunoglobulin recognized by a FcRn.

[00135] In some instances, at least one of the one or more linkers is located between the SARS-CoV-2 antigen and the Fc fragment of an immunoglobulin recognized by a FcRn.

[00136] In some instances, the one or more linkers are small, nonpolar, amino acid linkers. For example, the linker can be a GS-linker. The number of glycine, serine, and glycine/serine repeats can vary in the one or more linkers. Examples of GS linkers can be GSGSGS and GSGGGGSGGGGSGS. iv. Additional elements

In some aspects, the disclosed peptides comprise a signal peptide. In some aspects, a signal peptide is any short peptide (about 10-30 amino acids) that help translocate the peptide to the cell membrane. In some aspects, the signal peptide is present on the N-terminal end of the SARS-CoV-2 antigen (e.g. RBD protein). In some aspects, the signal peptide is derived from the coronavirus antigen. In some aspects, the signal peptide is derived from the SARS-CoV-2 antigen. For example, the native signal peptide found on SARS-CoV-2 S protein can be present in the disclosed peptides. In some aspects, the native signal peptide can comprise the amino acid sequence of MFVFLVLLPLVSSQC from SARS-CoV-2 S protein. In some aspects, a signal peptide can comprise one or more of the sequences present in Table 1.

[00137] In some aspects, the peptides disclosed herein can further comprise an adjuvant. In some aspects, the adjuvant is immunostimulatory oligonucleotides containing unmethylated CpG dinucleotides (“CpG”). CpGs are known in the art as being adjuvants when administered by both systemic and mucosal routes (WO 96/02555, EP 468520, Davis et al., J. Immunol, 1998, 160(2): 870-876, McCluskie and Davis, J. Immunol., 1998, 161(9): 4463-6). CpG is an abbreviation for cytosineguanosinc dinucicotide motifs present in DNA. Historically, it was observed that the DNA fraction of BCG could exert an anti -tumour effect. In further studies, synthetic oligonucleotides derived from BCG gene sequences were shown to be capable of inducing immunostimulatory effects (both in vitro and in vivo). The authors of these studies concluded that certain palindromic sequences, including a central CG motif, carried this activity. The central role of the CG motif in immunostimulation was later elucidated in a publication by Krieg, 1995, Nature 374, p. 546. Detailed analysis has shown that the CG motif has to be in a certain sequence context, and that such sequences are common in bacterial DNA but are rare in vertebrate DNA. The immunostimulatory sequence is often: Purine, Purine, C, G, pyrimidine, pyrimidine; wherein the dinucleotide CG motif is not methylated, but other unmethylated CpG sequences are known to be immunostimulatory and may be used in the present invention.

D. Peptide Complexes

[00138] Disclosed are peptide complexes comprising three of the disclosed peptides. For example, disclosed are peptide complexes comprising three peptides, wherein each of the three peptides comprises a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a coronavirus antigen; and a trimerization domain.

[00139] Also disclosed are peptide complexes comprising three peptides, wherein each of the three peptides comprises a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; SARS-CoV-2 antigen; and a trimerization domain. [00140] In some aspects, the peptide complexes are formed when the trimerization domain of the disclosed peptides causes trimerization. Thus, the three peptides can oligomerize at the trimerization domain.

[00141] In some aspects, disclosed are peptide complexes comprising three monomeric Fc fragments of an immunoglobulin recognized by a FcRn; three SARS-CoV-2 antigens; and three trimerization domains.

[00142] In some aspects, three of the disclosed peptides trimerize forming a peptide complex wherein each of the three peptides is oriented in the same direction. For example, the peptides trimerize with all of the monomeric Fc fragments of an immunoglobulin recognized by a FcRn on one end of the peptide complex and all of the SARS-CoV-2 antigens on the other end of the peptide complex.

[00143] In some aspects, each peptide of the peptide complex can comprise a different coronavirus antigen. For example, in some aspects, each peptide of the peptide complex can comprise a different SARS-CoV-2 spike protein fragment.

[00144] In another aspect, one or more of the peptides comprises an adjuvant instead of a coronavirus antigen. For example, two peptides of the peptide complex can comprise one of the disclosed peptides and the third peptide can be a peptide comprising a monomeric Fc fragment, a trimerization domain, and an adjuvant.

E. Nucleic Acid Sequences

[00145] As this specification discusses various peptide sequences it is understood that the nucleic acids that can encode those peptides are also disclosed. This would include all degenerate sequences related to a specific polypeptide sequence, i.e. all nucleic acids having a sequence that encodes one particular polypeptide sequence as well as all nucleic acids, including degenerate nucleic acids, encoding the disclosed variants and derivatives of the peptides. Thus, while each particular nucleic acid sequence may not be written out herein, it is understood that each and every sequence is in fact disclosed and described herein through the disclosed peptides. [00146] Disclosed are nucleic acid sequences capable of encoding any of the peptides disclosed herein. Further disclosed are nucleic acid constructs comprising the nucleic acid sequences capable of encoding any of the peptides disclosed herein.

[00147] Disclosed are vectors comprising a nucleic acid sequence capable of encoding peptides comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS-CoV-2 antigen; and a trimerization domain. In some instances, the peptide can be any of the peptides disclosed herein.

[00148] In some instances, the disclosed vectors can further comprise a nucleic acid sequence capable of encoding a tag (e.g. label or purification tag). In some aspects, the label can be any peptide or protein that is encoded for by a nucleic acid. For example, the labeling moiety can be, but is not limited to, GST, myc, His, or GFP.

[00149] In some instances, the labeling moiety can be operably linked to the nucleic acid sequence capable of encoding the peptides comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS-CoV-2 antigen; and a trimerization domain. Thus, the labeling moiety and the peptide can be transcribed together.

[00150] In addition to a nucleic acid sequence capable of encoding the disclosed peptides, the disclosed vectors can carry regulatory sequences that control the expression of the disclosed peptides in a host cell. It will be appreciated by those skilled in the art that the design of the vector, including the selection of regulatory sequences can depend on such factors as the choice of the host cell to be transformed, the level of expression of protein desired, etc. Preferred regulatory sequences for mammalian host cell expression include viral elements that direct high levels of protein expression in mammalian cells, such as promoters and/or enhancers derived from retroviral LTRs, cytomegalovirus (CMV) (such as the CMV promoter/enhancer), Simian Virus 40 (SV40) (such as the SV40 promoter/enhancer), adenovirus, (e.g., the adenovirus major late promoter (AdMLP)), polyoma and strong mammalian promoters such as native immunoglobulin and actin promoters. For further description of viral regulatory elements, and sequences thereof, see e.g., U.S. Pat. Nos. 5,168,062, 4,510,245 and 4,968,615. Methods of expressing polypeptides in bacterial cells or fungal cells, e.g., yeast cells, are also well known in the art.

[00151] In some instances, the disclosed vectors further comprise a promoter operably linked to the nucleic acid sequence capable of encoding the disclosed peptides. In some instances, the promoter can be an inducible promoter. In some instances, the promoter can be a cell-specific promoter. The nucleic acid sequence capable of encoding the disclosed peptides can be functionally linked to a promoter. By “functionally linked” is meant such that the promoter can promote expression of the nucleic acid sequence, thus having appropriate orientation of the promoter relative to the nucleic acid sequence.

[00152] In some instances, the nucleic acid sequence of a monomeric Fc fragment of a human IgGl can be

GAGCCTAAGTCCTGCGACAAGACCCACACAAGCCCACCATCTCCAGCTCCTGAGCT

GCTGGGAGGACCAAGCGTGTTCCTGTTTCCTCCAAAGCCTAAGGATACACTGATGA

TCTCTCGGACCCCAGAGGTGACATGCGTGGTGGTGGACGTGTCCCACGAGGACCCC

GAGGTGAAGTTTAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCTAAGACCAA GCCAAGGGAGGAGCAGTATAACAGCACATACCGGGTGGTGTCTGTGCTGACCGTGC T GC AT C AGGATT GGCT GA AC GGC A AGGA AT AC A AGT GC GC 7GT GAGC A AT A AGGC C

CTGCCAGCTCCCATCGAGAAGACAATCTCTAAGGCCAAGGGCCAGCCTAGAGAGCC ACAGGTGTATACCCTGCCACCTTCCCGCGACGAGCTGACCAAGAATCAGGTGAGCC TGACATGTCTGGTGAAGGGCTTCTACCCTAGCGATATCGCTGTGGAGTGGGAGTCTA ACGGCCAGCCAGAGAACAATTATAAGACCACACCACCCGTGCTGGACTCCGATGGC AGCTTCTTTCTGTACAGCAAGCTGACAGTGGACAAGTCTCGGTGGCAGCAGGGCAA CGTGTTCTCCTGCTCCGTGATGCATGAGGCCCTGCACAACCATTACACCCAGAAGAG CCTGTCTCTGTCCCCTGGCAAGtga (SEQ ID NO:9) or a variant thereof. In some aspects, the variant can a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 9. The dotted underline sequence AGC represents a cysteine to serine mutation (C226S in full length human IgGl) to produce a monomer human IgGl. The dotted underline sequence TCT represents a cysteine to serine mutation (C229S in full length human IgGl) to produce a monomer human IgGl. The italicized, underlined sequence represents a mutation preventing complement binding (K322A in full length human IgGl). The lowercase sequence represents a stop codon.

[00153] In some instances, the nucleic acid sequence of a monomeric Fc fragment of a mouse IgG2a can be

GAGCCCAGAGGGCCCACAATCAAGCCCTCTCCTCCATCCAAATCCCCAGCACCTAA

CCTCTTGGGTGGACCATCCGTCTTCATCTTCCCTCCAAAGATCAAGGATGTACTCAT

GATCTCCCTGAGCCCCATAGTCACATGTGTGGTGGTGGATGTGAGCGAGGATGACC

CAGATGTCCAGATCAGCTGGTTTGTGAACAACGTGGAAGTACACACAGCTCAGACA

C AAAC C CAT AGAGAGGATT AC AAC AGT ACTCT C C GGGT GGT C AGT GC C CTCC C CAT

CCAGCACCAGGACTGGATGAGTGGCAAGGCGTTCGCATGCGCGGTCAACAACAAA

GACCTCCCAGCGCCCATCGAGAGAACCATCTCAAAACCCAAAGGGTCAGTAAGAGC

TCCACAGGTATATGTCTTGCCTCCACCAGAAGAAGAGATGACTAAGAAACAGGTCA

CTCTGACCTGCATGGTCACAGACTTCATGCCTGAAGACATTTACGTGGAGTGGACCA

ACAACGGGAAAACAGAGCTAAACTACAAGAACACTGAACCAGTCCTGGACTCTGAT

GGTTCTTACTTCATGTACAGCAAGCTGAGAGTGGAAAAGAAGAACTGGGTGGAAAG

AAATAGCTACTCCTGTTCAGTGGTCCACGAGGGTCTGCACAATCACCACACGACTA

AGAGCTTCTCCCGGACTCCGGGTAAA (SEQ ID NO: 10) or a sequence 50%, 55%, 65%,

70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID

NO: 10. The bold underlined nucleic acids represent a mutation that encodes serine instead of cysteine to generate a single chain Fc. [00154] In some aspects, disclosed are nucleic acid sequences comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn sequence; a SARS-CoV-2 soluble S protein sequence; and a trimerization domain sequence. For example, disclosed are nucleic acid sequences comprising the sequence of

G G TA C CGCCACCATGTTCGTGTTTCTGGTGCTGCTGCCACTGGTGTCCAGCCAGTGC

GTGAACCTGACCACAAGAACCCAGCTGCCCCCTGCCTATACCAATTCTTTCACAAGA

GGCGTGTACTATCCAGACAAGGTGTTTCGCTCTTCCGTGCTGCACAGCACACAGGAT

CTGTTTCTGCCCTTCTTTTCTAACGTGACCTGGTTCCACGCCATCCACGTGTCCGGC A

CCAATGGCACAAAGAGGTTCGACAATCCTGTGCTGCCCTTCAACGATGGCGTGTAC

TTCGCTTCTACCGAGAAGTCCAACATCATCCGGGGCTGGATCTTTGGCACCACACTG

GACAGCAAGACACAGTCTCTGCTGATCGTGAACAATGCCACCAACGTGGTCATCAA

GGTGTGCGAGTTCCAGTTTTGTAATGATCCTTTCCTGGGCGTGTACTATCATAAGAA

CAATAAGTCCTGGATGGAGAGCGAGTTTCGCGTGTATAGCTCTGCTAACAATTGTAC

ATTTGAGTACGTGAGCCAGCCATTCCTGATGGACCTGGAGGGCAAGCAGGGCAATT

TCAAGAACCTGAGAGAGTTCGTGTTTAAGAATATCGATGGCTACTTCAAGATCTAC

AGCAAGCACACCCCTATCAACCTGGTGCGCGACCTGCCACAGGGCTTCTCTGCCCTG

GAGCCTCTGGTGGATCTGCCAATCGGCATCAACATCACCAGGTTTCAGACACTGCTG

GCTCTGCATCGGTCTTACCTGACACCTGGCGACTCCAGCTCTGGATGGACCGCTGGA

GCTGCTGCTTACTATGTGGGCTATCTGCAGCCAAGAACCTTCCTGCTGAAGTACAAC

GAGAATGGCACCATCACAGACGCCGTGGATTGCGCTCTGGATCCACTGTCCGAGAC

CAAGTGTACACTGAAGAGCTTTACCGTGGAGAAGGGCATCTATCAGACATCCAATT

TCAGAGTGCAGCCCACCGAGAGCATCGTGCGCTTTCCAAATATCACAAACCTG

TGCCCCTTTGGCGAGGTGTTCAACGCCACCCGCTTCGCTTCCGTGTACGCCTG

GAATAGAAAGCGCATCTCCAACTGCGTGGCTGACTATAGCGTGCTGTACAACT

CCGCCAGCTTCTCTACCTTTAAGTGCTATGGCGTGTCCCCCACAAAGCTGAAT

GACCTGTGCTTTACCAACGTGTACGCCGATAGCTTCGTGATCAGAGGCGACGA

GGTGCGCCAGATCGCTCCAGGACAGACAGGCAAGATCGCCGACTACAATTATA

AGCTGCCTGACGATTTCACCGGCTGCGTGATCGCTTGGAACTCCAACAATCTG

GATAGCAAAGTGGGCGGCAACTACAATTATCTGTACAGGCTGTTTCGGAAGAG

CAATCTGAAGCCTTTCGAGAGGGACATCTCTACAGAGATCTACCAGGCCGGCT

CCACCCCATGCAATGGCGTGGAGGGCTTTAACTGTTATTTCCCCCTGCAGTCTT

ACGGCTTCCAGCCTACCAACGGCGTGGGCTATCAGCCATACCGGGTGGTGGTG

CTGTCTTTTGAGCTGCTGCACGCTCCAGCTACAGTGTGCGGACCTAAGAAGTC

CACCAATCTGGTGAAGAACAAGTGCGTGAACTTCAACTTCAACGGACTGACCGG CACAGGCGTGCTGACCGAGAGCAACAAGAAGTTCCTGCCCTTTCAGCAGTTCGGCA

GGGACATCGCTGATACCACAGACGCCGTGCGGGACCCACAGACCCTGGAGATCCTG

GATATCACACCCTGCTCTTTCGGCGGCGTGTCCGTGATCACACCTGGCACCAATACA

TCTAACCAGGTGGCCGTGCTGTATCAGGACGTGAATTGTACCGAGGTGCCTGTGGC

CATCCACGCTGATCAGCTGACCCCAACATGGAGGGTGTACAGCACCGGCTCTAACG

TGTTTCAGACACGGGCTGGATGTCTGATCGGAGCTGAGCATGTGAACAATTCCTATG

AGTGCGACATCCCCATCGGCGCTGGCATCTGTGCCAGCTACCAGACCCAGACAAAC

AGCCCTAGGAGGGCTGC7TCTGTGGCTTCCCAGAGCATCATCGCCTATACCATGTCC

CTGGGCGCTGAGAATAGCGTGGCCTACTCCAACAATAGCATCGCTATCCCAACCAA

CTTCACAATCTCCGTGACCACAGAGATCCTGCCCGTGAGCATGACCAAGACATCTGT

GGACTGCACAATGTATATCTGTGGCGATTCTACCGAGTGCTCCAACCTGCTGCTGCA

GTACGGCAGCTTTTGTACCCAGCTGAATAGGGCTCTGACAGGCATCGCCGTGGAGC

AGGATAAGAACACACAGGAGGTGTTCGCCCAGGTGAAGCAGATCTACAAGACCCC

ACCCATCAAGGACTTTGGCGGCTTCAACTTCTCCCAGATCCTGCCTGATCCATCTAA

GCCCTCCAAGGC7A££TTTATCGAGGACCTGCTGTTCAACAAGGTGACCCTGGCT G

ATGCCGGCTTCATCAAGCAGTATGGCGATTGCCTGGGCGACATCGCTGCCAGGGAC

CTGATCTGTGCTCAGAAGTTTAATGGCCTGACCGTGCTGCCTCCACTGCTGACAGAT

GAGATGATCGCCCAGTACACATCTGCCCTGCTGGCTGGCACCATCACATCCGGATG

GACCTTCGGCGCTGGAGCTGCCCTGCAGATCCCTTTTGCTATGCAGATGGCCTATCG

GTTCAACGGCATCGGCGTGACCCAGAATGTGCTGTACGAGAACCAGAAGCTGATCG

CTAATCAGTTTAACTCCGCCATCGGCAAGATCCAGGACTCTCTGTCCAGCACAGCTT

CCGCCCTGGGCAAGCTGCAGGATGTGGTGAATCAGAACGCTCAGGCCCTGAATACC

CTGGTGAAGCAGCTGTCTTCCAACTTCGGCGCTATCAGCTCTGTGCTGAATGATATC

CT G AGC AG ACTGG AC GC4CXTG AGGCT G AGGT GC AG AT C G AC AGGCTG AT C AC AGG

CCGGCTGCAGAGCCTGCAGACCTACGTGACACAGCAGCTGATCAGAGCTGCCGAGA

TCCGCGCTTCTGCCAACCTGGCTGCCACCAAGATGTCTGAGTGCGTGCTGGGCCAGT

CCAAGCGCGTGGACTTTTGTGGCAAGGGCTATCACCTGATGAGCTTCCCCCAGTCTG

CTCCTCACGGCGTGGTGTTTCTGCATGTGACCTACGTGCCCGCCCAGGAGAAGAACT

TCACCACAGCTCCTGCCATCTGCCACGATGGCAAGGCCCATTTTCCCAGAGAGGGC

GTGTTCGTGTCTAACGGCACCCATTGGTTTGTGACACAGCGCAATTTCTACGAGCCT

CAGATCATCACCACAGACAATACCTTCGTGTCCGGCAACTGTGACGTGGTCATCGG

CATCGTGAACAATACCGTGTATGATCCCCTGCAGCCTGAGCTGGACTCTTTTAAGGA

GGAGCTGGATAAGTACTTCAAGAATCACACCTCCCCAGACGTGGATCTGGGCGACA

TCTCCGGCATCAATGCTAGCGTGGTGAACATCCAGAAGGAGATCGACAGGCTGAAC GAGGTGGCCAAGAATCTGAACGAGTCTCTGATCGATCTGCAGGAGCTGGGCAAGTA TGAGCAGTACATCAAGTGGCCAGGATCTGGATCCGGCAGCAGGTCTCTGGTGCCAC GGGGCTCTCCAGGATCCGGATATATCCCAGAGGCTCCCAGAGACGGACAGGCTTAC GTGCGCAAGGATGGCGAGTGGGTGCTGCTGTCCACCTTCCTGGGCGGYTC/GOYlGG/l G GAG GTCCGGAG AGGAGGATCCCGGCAC,CGXGCCTXXGTCCTGCGXCXXGXCCC ACACAAGCCCACCATCTCCAGCTCCTGAGCTGCTGGGAGGACCAAGCGTGTTC CTGTTTCCTCCAAAGCCTAAGGATACACTGATGATCTCTCGGACCCCAGAGGT GACATGCGTGGTGGTGGACGTGTCCCACGAGGACCCCGAGGTGAAGTTTAACT GGTACGTGGACGGCGTGGAGGTGCATAATGCTAAGACCAAGCCAAGGGAGGA GCAGTATAACAGCACATACCGGGTGGTGTCTGTGCTGACCGTGCTGCATCAGG ATTGGCTGAACGGCAAGGAATACAAGTGCGCTGTGAGCAATAAGGCCCTGCCA GCTCCCATCGAGAAGACAATCTCTAAGGCCAAGGGCCAGCCTAGAGAGCCACA GGTGTATACCCTGCCACCTTCCCGCGACGAGCTGACCAAGAATCAGGTGAGCC TGACATGTCTGGTGAAGGGCTTCTACCCTAGCGATATCGCTGTGGAGTGGGAG TCTAACGGCCAGCCAGAGAACAATTATAAGACCACACCACCCGTGCTGGACTC CGATGGCAGCTTCTTTCTGTACAGCAAGCTGACAGTGGACAAGTCTCGGTGGC AGCAGGGCAACGTGTTCTCCTGCTCCGTGATGCATGAGGCCCTGCACAACCAT TACACCCAGAAGAGCCTGTCTCTGTCCCCTGGCAAGtgaC?UGAG (SEP ID NO 2) or a variant thereof. In some aspects, the variant can a sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:2. The double underlined sequence represents a Kpnl cloning site. The shaded sequence represents a Kozak sequence. The underlined sequence represents a native signal peptide of S protein. The bold shaded sequence represents the RBD of SI. The bold underline sequence represents the mutated S1/S2 cleavage site (R685A in italics, no change in S686). The bold letter and bold underline sequence represents a mutation at the S2’ cleavage site (R816A in italics, no change in S817). The bold, italics, and shaded sequence represents K986P and V987P mutations which allow the S protein to keep the Pre-fusion conformation. The dotted underline and shaded sequence represents a 6GS (glycine-serine) linker. The double squiggle underline represents the foldon domain from T4 fibrin. The dotted _. underline, italicized shaded sequence represents a 14GS (glycine-serine) linker. The bold sequence is human IgGl. The dptted_underlme sequence AGC represents a cysteine to serine mutation (C226S of full length human IgGl, Cl IS of the Fc fragment disclosed herein) in human IgGl to produce a monomer human IgGl. The dotted underline sequence TCT represents a cysteine to serine mutation (C229S of full length human IgGl, C14S of the Fc fragment disclosed herein) in human IgGl to produce a monomer human IgGl. The italicized, underlined sequence represents a mutation preventing complement binding (K322A of full length human IgGl, K107A of the Fc fragment disclosed herein) in human IgGl. The bold lowercase sequence represents a stop codon in IgGl. The squiggly underline represents an Xhol cloning site. Nucleic acids 58 to 3594 represent the SARS-Cov-2 spike protein.

Nucleic acids 3697-3783 represent the foldon domain of T4 fibrin. Nucleic acids 3829-4527 represent a monomeric Fc IgGl fragment.

[00155] In some aspects, disclosed are nucleic acid sequences comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn sequence; a SARS-CoV-2 SI protein sequence; and a trimerization domain sequence. For example, disclosed are nucleic acid sequences comprising the sequence of

GG7XCCGCCACCATGTTCGTGTTTCTGGTGCTGCTGCCACTGGTGTCCAGCCAGTGC

GTGAACCTGACCACAAGAACCCAGCTGCCCCCTGCCTATACCAATTCTTTCACAAGA

GGCGTGTACTATCCAGACAAGGTGTTTCGCTCTTCCGTGCTGCACAGCACACAGGAT

CTGTTTCTGCCCTTCTTTTCTAACGTGACCTGGTTCCACGCCATCCACGTGTCCGGC A

CCAATGGCACAAAGAGGTTCGACAATCCTGTGCTGCCCTTCAACGATGGCGTGTAC

TTCGCTTCTACCGAGAAGTCCAACATCATCCGGGGCTGGATCTTTGGCACCACACTG

GACAGCAAGACACAGTCTCTGCTGATCGTGAACAATGCCACCAACGTGGTCATCAA

GGTGTGCGAGTTCCAGTTTTGTAATGATCCTTTCCTGGGCGTGTACTATCATAAGAA

CAATAAGTCCTGGATGGAGAGCGAGTTTCGCGTGTATAGCTCTGCTAACAATTGTAC

ATTTGAGTACGTGAGCCAGCCATTCCTGATGGACCTGGAGGGCAAGCAGGGCAATT

TCAAGAACCTGAGAGAGTTCGTGTTTAAGAATATCGATGGCTACTTCAAGATCTAC

AGCAAGCACACCCCTATCAACCTGGTGCGCGACCTGCCACAGGGCTTCTCTGCCCTG

GAGCCTCTGGTGGATCTGCCAATCGGCATCAACATCACCAGGTTTCAGACACTGCTG

GCTCTGCATCGGTCTTACCTGACACCTGGCGACTCCAGCTCTGGATGGACCGCTGGA

GCTGCTGCTTACTATGTGGGCTATCTGCAGCCAAGAACCTTCCTGCTGAAGTACAAC

GAGAATGGCACCATCACAGACGCCGTGGATTGCGCTCTGGATCCACTGTCCGAGAC

CAAGTGTACACTGAAGAGCTTTACCGTGGAGAAGGGCATCTATCAGACATCCAATT

TCAGAGTGCAGCCCACCGAGAGCATCGTGCGCTTTCCAAATATCACAAACCTG

TGCCCCTTTGGCGAGGTGTTCAACGCCACCCGCTTCGCTTCCGTGTACGCCTG

GAATAGAAAGCGCATCTCCAACTGCGTGGCTGACTATAGCGTGCTGTACAACT

CCGCCAGCTTCTCTACCTTTAACTGCTATGCCGTCTCCCCCACAAACCTCAAT

GACCTGTGCTTTACCAACGTGTACGCCGATAGCTTCGTGATCAGAGGCGACGA

GGTGCGCCAGATCGCTCCAGGACAGACAGGCAAGATCGCCGACTACAATTATA

AGCTGCCTGACGATTTCACCGGCTGCGTGATCGCTTGGAACTCCAACAATCTG GATAGCAAAGTGGGCGGCAACTACAATTATCTGTACAGGCTGTTTCGGAAGAG

CAATCTCAAGCCTTTCGAGAGGGACATCTCTACAGAGATCTACCAGCCCCGCT

CCACCCCATGCAATGGCGTGGAGGGCTTTAACTGTTATTTCCCCCTGCAGTCTT

ACGGCTTCCAGCCTACCAACGGCGTGGGCTATCAGCCATACCGGGTGGTGGTG

CTGTCTTTTGAGCTGCTGCACGCTCCAGCTACAGTGTGCGGACCTAAGAAGTC

CACCAATCTGGTGAAGAACAAGTGCGTGAACTTCAACTTCAACGGACTGACCGG

CACAGGCGTGCTGACCGAGAGCAACAAGAAGTTCCTGCCCTTTCAGCAGTTCGGCA

GGGACATCGCTGATACCACAGACGCCGTGCGGGACCCACAGACCCTGGAGATCCTG

GATATCACACCCTGCTCTTTCGGCGGCGTGTCCGTGATCACACCTGGCACCAATACA

TCTAACCAGGTGGCCGTGCTGTATCAGGACGTGAATTGTACCGAGGTGCCTGTGGC

CATCCACGCTGATCAGCTGACCCCAACATGGAGGGTGTACAGCACCGGCTCTAACG

TGTTTCAGACACGGGCTGGATGTCTGATCGGAGCTGAGCATGTGAACAATTCCTATG

AGTGCGACATCCCCATCGGCGCTGGCATCTGTGCCAGCTACCAGACCCAGACAAAC

AGCCCTAGGAGGGCTGC7GGATCTGGATCCGGCAGCAGGTCTCTGGTGCCACGGGG

CTCTCCAGGATCCGGATATATCCCAGAGGCTCCCAGAGACGGACAGGCTTACGTGC

GCAAGGATGGCGAGTGGGTGCTGCTGTCCACCTTCCTGGGCGGCTCTGGA GGA GG AG

GYTC CG G AGG AG GAG G ATC CGGC AGC GAGCCTAAGTCCTGCGACAAGACCCACAC

AAGCCCACCATCTCCAGCTCCTGAGCTGCTGGGAGGACCAAGCGTGTTCCTGT

TTCCTCCAAAGCCTAAGGATACACTGATGATCTCTCGGACCCCAGAGGTGACA

TGCGTGGTGGTGGACGTGTCCCACGAGGACCCCGAGGTGAAGTTTAACTGGTA

CGTGGACGGCGTGGAGGTGCATAATGCTAAGACCAAGCCAAGGGAGGAGCAG

TATAACAGCACATACCGGGTGGTGTCTGTGCTGACCGTGCTGCATCAGGATTG

GCTGAACGGCAAGGAATACAAGTGCGCTGTGAGCAATAAGGCCCTGCCAGCTC

CCATCGAGAAGACAATCTCTAAGGCCAAGGGCCAGCCTAGAGAGCCACAGGTG

TATACCCTGCCACCTTCCCGCGACGAGCTGACCAAGAATCAGGTGAGCCTGAC

ATGTCTGGTGAAGGGCTTCTACCCTAGCGATATCGCTGTGGAGTGGGAGTCTA

ACGGCCAGCCAGAGAACAATTATAAGACCACACCACCCGTGCTGGACTCCGAT

GGCAGCTTCTTTCTGTACAGCAAGCTGACAGTGGACAAGTCTCGGTGGCAGCA

GGGCAACGTGTTCTCCTGCTCCGTGATGCATGAGGCCCTGCACAACCATTACA

CCCAGAAGAGCCTGTCTCTGTCCCCTGGCAAGtgaCTCGAG(SEQID NO4)or a variant sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 4. The double underlined sequence represents a Kpnl cloning site. The shaded sequence represents a Kozak sequence. The underlined sequence represents a native signal peptide of S protein. The bold shaded sequence represents the RBD of SI. The italics and bold underline sequence represents the mutated S1/S2 cleavage site (R685A of S protein in italics). The dotted underline and shaded sequence represents a 6GS (glycine- serine) linker. The double squiggle underline represents the foldon domain from T4 fibrin. The dotted underline, italicized shaded sequence represents a 14GS (glycine-serine) linker. The bold sequence is human IgGl. The dotted underline sequence AGC represents a cysteine to serine mutation (C226S of full length human IgGl, Cl IS of the Fc fragment disclosed herein) in human IgGl to produce a monomer human IgGl. The dotted underline sequence TCT represents a cysteine to serine mutation (C229S of full length human IgGl, C14S of the Fc fragment disclosed herein) in human IgGl to produce a monomer human IgGl. The italicized, underlined sequence represents a mutation preventing complement binding (K322A of full length human IgGl, K107A of the Fc fragment disclosed herein) in human IgGl. The bold lowercase sequence represents a stop codon in IgGl. The squiggly underline represents an Xhol cloning site. Nucleic acids 58 to 2067 represent the SARS-Cov-2 SI protein sequence. Nucleic acids 2113 to 2199 represent the foldon domain of T4 fibrin. Nucleic acids 2245 to 2943 represent a monomeric Fc IgGl fragment.

[00156] In some aspects, disclosed are nucleic acid sequences comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn sequence; a SARS-CoV-2 RBD protein sequence; and a trimerization domain sequence. For example, disclosed are nucleic acid sequences comprising the sequence of

GGTA ( Y GCC ACC AT GTT C GT GTTT CT GGTGCT GCT GC C ACTGGT GT C C AGC C AGT GC

GTGAGAGTGCAGCCCACCGAGAGCATCGTGCGCTTTCCAAATATCACAAACCT

GTCCCCCTTTGCCGAGGTGTTCAACGCCACCCGCTTCGCTTCCGTCTACCCCT

GGAATAGAAAGCGCATCTCCAACTGCGTGGCTGACTATAGCGTGCTGTACAAC

TCCGCCAGCTTCTCTACCTTTAAGTGCTATGGCGTGTCCCCCACAAAGCTGAAT

CACCTCTGCTTTACCAACCTGTACGCCGATAGCTTCGTCATCAGACGCCACGA

GGTGCGCCAGATCGCTCCAGGACAGACAGGCAAGATCGCCGACTACAATTATA

AGCTGCCTGACGATTTCACCGGCTGCGTGATCGCTTGGAACTCCAACAATCTG

GATAGCAAACTGGGCGGCAACTACAATTATCTCTACACGCTGTTTCGGAACAG

CAATCTGAAGCCTTTCGAGAGGGACATCTCTACAGAGATCTACCAGGCCGGCT

CCACCCCATGCAATGGCGTGGAGGGCTTTAACTGTTATTTCCCCCTGCAGTCTT

ACGCCTTCCAGCCTACCAACGGCGTGGGCTATCAGCCATACCGGGTCGTCGTG

CTGTCTTTTGAGCTGCTGCACGCTCCAGCTACAGTGTGCGGACCTAAGAAGTC

CACCAATCTGGTGAAGAACAAGTGCGTGAACTTCGGATCTGGATCCGGC-AGCAG

GTCTCTGGTGCCACGGGGCTCTCCAGGATCCGGATATATCCCAGAGGCTCCCAGAG ACGGACAGGCTTACGTGCGCAAGGATGGCGAGTGGGTGCTGCTGTCCACCTTCCTG

GGCGGCTCTGGAG GAGGAGGATCCGGAGGAGGAGGATCCGGC AGCGAGCCTAAGTC

CTGCGACAAGACCCACACAAGCCCACCATCTCCAGCTCCTGAGCTGCTGGGAG

GACCAAGCGTGTTCCTGTTTCCTCCAAAGCCTAAGGATACACTGATGATCTCTC

GGACCCCAGAGGTGACATGCGTGGTGGTGGACGTGTCCCACGAGGACCCCGA

GGTGAAGTTTAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCTAAGACCA

AGCCAAGGGAGGAGCAGTATAACAGCACATACCGGGTGGTGTCTGTGCTGACC

GTGCTGCATCAGGATTGGCTGAACGGCAAGGAATACAAGTGCGCTGTGAGCAA

TAAGGCCCTGCCAGCTCCCATCGAGAAGACAATCTCTAAGGCCAAGGGCCAGC

CTAGAGAGCCACAGGTGTATACCCTGCCACCTTCCCGCGACGAGCTGACCAAG

AATCAGGTGAGCCTGACATGTCTGGTGAAGGGCTTCTACCCTAGCGATATCGC

TGTGGAGTGGGAGTCTAACGGCCAGCCAGAGAACAATTATAAGACCACACCAC

CCGTGCTGGACTCCGATGGCAGCTTCTTTCTGTACAGCAAGCTGACAGTGGAC

AAGTCTCGGTGGCAGCAGGGCAACGTGTTCTCCTGCTCCGTGATGCATGAGGC

CCTGCACAACCATTACACCCAGAAGAGCCTGTCTCTGTCCCCTGGCAAGtgaCTU

GAG (SEQ ID NO: 6) or a variant sequence 50%, 55%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:6.

[00157] The double underlined sequence represents a Kpnl cloning site. The shaded sequence represents a Kozak sequence. The underlined sequence represents a native signal peptide of S protein. The bold shaded sequence represents the RBD of SI.

[00158] The dotted underline and shaded sequence represents a 6GS (glycine-serine) linker. The double squiggle underline represents the foldon domain from T4 fibrin. The dotted underline, italicized shaded sequence represents a 14GS (glycine-serine) linker. The bold sequence is human IgGl. The dotted underline sequence AGC represents a cysteine to serine mutation (C226S of full length human IgGl, Cl IS of the Fc fragment disclosed herein) in human IgGl to produce a monomer human IgGl. The dotted underline sequence TCT represents a cysteine to serine mutation (C229S of full length human IgGl, C14S of the Fc fragment disclosed herein) in human IgGl to produce a monomer human IgGl. The italicized, underlined sequence represents a mutation preventing complement binding (K322A of full length human IgGl, K107A of the Fc fragment disclosed herein) in human IgGl. The bold lowercase sequence represents a stop codon in IgGl. The squiggly underline represents an Xhol cloning site. Nucleic acids 61 to 729 represent the SARS-Cov-2 RBD protein sequence. Nucleic acids 775 to 861 represent the foldon domain of T4 fibrin. Nucleic acids 907 to 1605 represent a monomeric Fc IgGl fragment. F. Compositions

[00159] Disclosed are compositions comprising any of the disclosed peptides, peptide complexes, nucleic acid sequences, or vectors. In some instances, disclosed are compositions comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a coronavirus antigen; and a trimerization domain. Also disclosed are compositions comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS-CoV-2 antigen; and a trimerization domain.

[00160] In some instances, the composition can be a vaccine.

[00161] In some instances, the compositions can further comprise a pharmaceutically acceptable carrier. By “pharmaceutically acceptable” is meant a material or carrier that would be selected to minimize any degradation of the active ingredient and to minimize any adverse side effects in the subject, as would be well known to one of skill in the art. The pharmaceutical carrier employed can be, for example, a solid, liquid, or gas. Examples of solid carriers include lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, and stearic acid. Examples of liquid carriers are sugar syrup, peanut oil, olive oil, and water. Examples of gaseous carriers include carbon dioxide and nitrogen. Examples of pharmaceutically acceptable carriers include dimyristoylphosphatidyl (DMPC), phosphate buffered saline or a multivesicular liposome. For example, PG: PC: Cholesterol: peptide or PC:peptide can be used as carriers in this invention. Other suitable pharmaceutically acceptable carriers and their formulations are described in Remington: The Science and Practice of Pharmacy (19th ed.) ed. A.R. Gennaro, Mack Publishing Company, Easton, PA 1995. Typically, an appropriate amount of pharmaceutically-acceptable salt is used in the formulation to render the formulation isotonic. Other examples of the pharmaceutically-acceptable carrier include, but are not limited to, saline, Ringer’s solution and dextrose solution. The pH of the solution can be from about 5 to about 8, or from about 7 to about 7.5. Further carriers include sustained release preparations such as semi-permeable matrices of solid hydrophobic polymers containing the composition, which matrices are in the form of shaped articles, e.g., films, stents (which are implanted in vessels during an angioplasty procedure), liposomes or microparticles. It will be apparent to those persons skilled in the art that certain carriers may be more preferable depending upon, for instance, the route of administration and concentration of composition being administered.

These most typically would be standard carriers for administration of drugs to humans, including solutions such as sterile water, saline, and buffered solutions at physiological pH. [00162] In order to enhance the solubility and/or the stability of the disclosed peptides in pharmaceutical compositions, it can be advantageous to employ a-, b- or g-cyclodextrins or their derivatives, in particular hydroxyalkyl substituted cyclodextrins, e.g. 2-hydroxypropyl-P- cyclodextrin or sulfobutyl-P-cyclodextrin. Also, co-solvents such as alcohols may improve the solubility and/or the stability of the compounds according to the invention in pharmaceutical compositions.

[00163] Pharmaceutical compositions can also include carriers, thickeners, diluents, buffers, preservatives and the like, as long as the intended activity of the polypeptide, peptide, nucleic acid, vector of the invention is not compromised. Pharmaceutical compositions may also include one or more active ingredients (in addition to the composition of the invention) such as antimicrobial agents, anti-inflammatory agents, anesthetics, and the like. The pharmaceutical composition may be administered in a number of ways depending on whether local or systemic treatment is desired, and on the area to be treated.

[00164] Preparations of parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media. Parenteral vehicles include sodium chloride solution, Ringer’s dextrose, dextrose and sodium chloride, lactated Ringer’s, or fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer’s dextrose), and the like. Preservatives and other additives may also be present such as, for example, antimicrobials, anti-oxidants, chelating agents, and inert gases and the like.

[00165] Formulations for optical administration may include ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable.

[00166] Compositions for oral administration include powders or granules, suspensions or solutions in water or non-aqueous media, capsules, sachets, or tablets. Thickeners, flavorings, diluents, emulsifiers, dispersing aids, or binders may be desirable. Some of the compositions may potentially be administered as a pharmaceutically acceptable acid- or base- addition salt, formed by reaction with inorganic acids such as hydrochloric acid, hydrobromic acid, perchloric acid, nitric acid, thiocyanic acid, sulfuric acid, and phosphoric acid, and organic acids such as formic acid, acetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, oxalic acid, malonic acid, succinic acid, maleic acid, and fumaric acid, or by reaction with an inorganic base such as sodium hydroxide, ammonium hydroxide, potassium hydroxide, and organic bases such as mon-, di-, trialkyl and aryl amines and substituted ethanolamines.

[00167] Because of the ease in administration, oral administration can be used, and tablets and capsules represent the most advantageous oral dosage unit forms in which case solid pharmaceutical carriers are obviously employed. In preparing the compositions for oral dosage form, any convenient pharmaceutical media can be employed. For example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like can be used to form oral liquid preparations such as suspensions, elixirs and solutions; while carriers such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents, and the like can be used to form oral solid preparations such as powders, capsules and tablets. Because of their ease of administration, tablets and capsules are the preferred oral dosage units whereby solid pharmaceutical carriers are employed. Optionally, tablets can be coated by standard aqueous or nonaqueous techniques.

[00168] A tablet containing the compositions of the present invention can be prepared by compression or molding, optionally with one or more accessory ingredients or adjuvants. Compressed tablets can be prepared by compressing, in a suitable machine, the active ingredient in a free-flowing form such as powder or granules, optionally mixed with a binder, lubricant, inert diluent, surface active or dispersing agent. Molded tablets can be made by molding in a suitable machine, a mixture of the powdered compound moistened with an inert liquid diluent. [00169] The disclosed peptides can be formulated and/or administered in or with a pharmaceutically acceptable carrier. As used herein, the term “pharmaceutically acceptable carrier” refers to sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like), carboxymethylcellulose and suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants. These compositions can also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents such as paraben, chlorobutanol, phenol, sorbic acid and the like. It can also be desirable to include isotonic agents such as sugars, sodium chloride and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the inclusion of agents, such as aluminum monostearate and gelatin, which delay absorption. Injectable depot forms are made by forming microencapsule matrices of the drug (e.g. peptide) in biodegradable polymers such as polylactide-polyglycolide, poly(orthoesters) and poly(anhydrides). Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions that are compatible with body tissues. The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable media just prior to use. Suitable inert carriers can include sugars such as lactose. Desirably, at least 95% by weight of the particles of the active ingredient have an effective particle size in the range of 0.01 to 10 micrometers.

[00170] Thus, the compositions disclosed herein can comprise lipids such as liposomes, such as cationic liposomes (e.g., DOTMA, DOPE, DC-cholesterol) or anionic liposomes. Liposomes can further comprise proteins to facilitate targeting a particular cell, if desired. Administration of a composition comprising a peptide and a cationic liposome can be administered to the blood, to a target organ, or inhaled into the respiratory tract to target cells of the respiratory tract. For example, a composition comprising a peptide or nucleic acid sequence described herein and a cationic liposome can be administered to a subject's lung cells. Regarding liposomes, see, e.g., Brigham et al. Am. J. Resp. Cell. Mol. Biol. 1:95 100 (1989); Feigner et al. Proc. Natl. Acad. Sci USA 84:7413 7417 (1987); U.S. Patent No. 4,897,355. Furthermore, the compound can be administered as a component of a microcapsule that can be targeted to specific cell types, such as macrophages, or where the diffusion of the compound or delivery of the compound from the microcapsule is designed for a specific rate or dosage.

[00171] In some instances, disclosed are pharmaceutical compositions comprising any of the disclosed peptides, peptide complexes, nucleic acid sequences or vectors described herein, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier, buffer, or diluent. In various aspects, the peptide of the pharmaceutical composition is encapsulated in a delivery vehicle. In a further aspect, the delivery vehicle is a liposome, a microcapsule, or a nanoparticle. In a still further aspect, the delivery vehicle is PEG-ylated. [00172] In the methods described herein, delivery of the compositions to cells can be via a variety of mechanisms. As defined above, disclosed herein are compositions comprising any one or more of the peptides described herein and can also include a carrier such as a pharmaceutically acceptable carrier. For example, disclosed are pharmaceutical compositions, comprising the peptides disclosed herein, and a pharmaceutically acceptable carrier. In one aspect, disclosed are pharmaceutical compositions comprising the disclosed peptides, peptide complexes, nucleic acid sequences or vectors. That is, a pharmaceutical composition can be provided comprising a therapeutically effective amount of at least one disclosed peptide or at least one product of a disclosed method and a pharmaceutically acceptable carrier.

[00173] In certain aspects, the disclosed pharmaceutical compositions comprise the disclosed peptides (including pharmaceutically acceptable salt(s) thereof) as an active ingredient, a pharmaceutically acceptable carrier, and, optionally, other therapeutic ingredients or adjuvants. The instant compositions include those suitable for nasal, oral, rectal, topical, and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most suitable route in any given case will depend on the particular host, and nature and severity of the conditions for which the active ingredient is being administered. The pharmaceutical compositions can be conveniently presented in unit dosage form and prepared by any of the methods well known in the art of pharmacy.

[00174] In practice, the peptides described herein, or pharmaceutically acceptable salts thereof, of this invention can be combined as the active ingredient in intimate admixture with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier can take a wide variety of forms depending on the form of preparation desired for administration, e.g., oral or parenteral (including intravenous). Thus, the pharmaceutical compositions of the present invention can be presented as discrete units suitable for oral administration such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient. Further, the compositions can be presented as a powder, as granules, as a solution, as a suspension in an aqueous liquid, as a non-aqueous liquid, as an oil-in-water emulsion or as a water-in-oil liquid emulsion. In addition to the common dosage forms set out above, the compounds of the invention, and/or pharmaceutically acceptable salt(s) thereof, can also be administered by controlled release means and/or delivery devices. The compositions can be prepared by any of the methods of pharmacy. In general, such methods include a step of bringing into association the active ingredient with the carrier that constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and intimately admixing the active ingredient with liquid carriers or finely divided solid carriers or both. The product can then be conveniently shaped into the desired presentation.

[00175] The peptides, peptide complexes, nucleic acid sequences, or vectors described herein, or pharmaceutically acceptable salts thereof, can also be included in pharmaceutical compositions in combination with one or more other therapeutically active compounds.

[00176] Pharmaceutical compositions of the present invention suitable for parenteral administration can be prepared as solutions or suspensions of the active compounds in water. A suitable surfactant can be included such as, for example, hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof in oils. Further, a preservative can be included to prevent the detrimental growth of microorganisms. [00177] Pharmaceutical compositions of the present invention suitable for injectable use include sterile aqueous solutions or dispersions. Furthermore, the compositions can be in the form of sterile powders for the extemporaneous preparation of such sterile injectable solutions or dispersions. Typically, the final injectable form should be sterile and should be effectively fluid for easy syringability. The pharmaceutical compositions should be stable under the conditions of manufacture and storage; thus, preferably should be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol and liquid polyethylene glycol), vegetable oils, and suitable mixtures thereof.

[00178] Injectable solutions, for example, can be prepared in which the carrier comprises saline solution, glucose solution or a mixture of saline and glucose solution. Injectable suspensions may also be prepared in which case appropriate liquid carriers, suspending agents and the like may be employed. Also included are solid form preparations that are intended to be converted, shortly before use, to liquid form preparations.

[00179] Pharmaceutical compositions of the present invention can be in a form suitable for topical use such as, for example, an aerosol, cream, ointment, lotion, dusting powder, mouth washes, gargles, and the like. Further, the compositions can be in a form suitable for use in transdermal devices. These formulations can be prepared, utilizing a compound of the invention, or pharmaceutically acceptable salts thereof, via conventional processing methods. As an example, a cream or ointment is prepared by mixing hydrophilic material and water, together with about 5 wt% to about 10 wt% of the compound, to produce a cream or ointment having a desired consistency.

[00180] In the compositions suitable for percutaneous administration, the carrier optionally comprises a penetration enhancing agent and/or a suitable wetting agent, optionally combined with suitable additives of any nature in minor proportions, which additives do not introduce a significant deleterious effect on the skin. Said additives may facilitate the administration to the skin and/or may be helpful for preparing the desired compositions. These compositions may be administered in various ways, e.g., as a transdermal patch, as a spot on, as an ointment.

[00181] Pharmaceutical compositions of this invention can be in a form suitable for rectal administration wherein the carrier is a solid. It is preferable that the mixture forms unit dose suppositories. Suitable carriers include cocoa butter and other materials commonly used in the art. The suppositories can be conveniently formed by first admixing the composition with the softened or melted carrier(s) followed by chilling and shaping in molds.

[00182] In addition to the aforementioned carrier ingredients, the pharmaceutical formulations described above can include, as appropriate, one or more additional carrier ingredients such as diluents, buffers, flavoring agents, binders, surface-active agents, thickeners, lubricants, preservatives (including anti-oxidants) and the like. Furthermore, other adjuvants can be included to render the formulation isotonic with the blood of the intended recipient. Compositions containing a disclosed peptide, and/or pharmaceutically acceptable salts thereof, can also be prepared in powder or liquid concentrate form.

[00183] The exact dosage and frequency of administration depends on the particular disclosed peptide, a product of a disclosed method of making, a pharmaceutically acceptable salt, solvate, or polymorph thereof, a hydrate thereof, a solvate thereof, a polymorph thereof, or a stereochemically isomeric form thereof; the particular condition being treated and the severity of the condition being treated; various factors specific to the medical history of the subject to whom the dosage is administered such as the age; weight, sex, extent of disorder and general physical condition of the particular subject, as well as other medication the individual may be taking; as is well known to those skilled in the art. Furthermore, it is evident that said effective daily amount may be lowered or increased depending on the response of the treated subject and/or depending on the evaluation of the physician prescribing the compositions.

[00184] Depending on the mode of administration, the pharmaceutical composition will comprise from 0.05 to 99 % by weight, preferably from 0.1 to 70 % by weight, more preferably from 0.1 to 50 % by weight of the active ingredient, and, from 1 to 99.95 % by weight, preferably from 30 to 99.9 % by weight, more preferably from 50 to 99.9 % by weight of a pharmaceutically acceptable carrier, all percentages being based on the total weight of the composition.

G. Methods

[00185] Disclosed are methods for eliciting a protective immune response against coronavirus, methods of treating or preventing coronavirus infection and methods of reducing coronavirus viral titers in a subject infected with coronavirus. Each of these methods comprise administering an effective amount of a composition comprising any of the peptides, peptide complexes, nucleic acids or vectors disclosed herein. As an example, each of these methods is further described below with regards to the coronavirus being SARS-CoV-2 and using the specific coronavirus antigen, a SARS-CoV-2 S antigen.

[00186] Disclosed are methods for eliciting a protective immune response against SARS- CoV-2 comprising administering to a subject an effective amount of a composition comprising any of the peptides, peptide complexes, nucleic acids or vectors disclosed herein.

[00187] Disclosed are methods for eliciting a protective immune response against SARS- CoV-2 comprising administering to a subject an effective amount of a composition comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS-CoV-2 antigen; and a trimerization domain, wherein the administering is to a mucosal epithelium.

[00188] Disclosed are methods for eliciting a protective immune response against SARS- CoV-2 comprising administering to a subject an effective amount of a composition comprising a peptide complex, wherein the peptide complex comprises three peptides forming a trimer, wherein each of the three peptides comprises a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS-CoV-2 antigen; and a trimerization domain, wherein the administering is to a mucosal epithelium.

[00189] Disclosed are methods of treating or preventing SARS-CoV-2 infection in a subject. Disclosed are methods of treating a subject exposed to SARS-CoV-2 or at risk of being exposed to SARS-CoV-2 comprising administering to a subject an effective amount of a composition comprising any of the peptides, peptide complexes, nucleic acids or vectors disclosed herein. [00190] Disclosed are methods of treating a subject exposed to SARS-CoV-2 or at risk of being exposed to SARS-CoV-2 comprising administering to the subject an effective amount of a composition comprising a peptide complex, wherein the peptide complex comprises three peptides forming a trimer, wherein each of the three peptides comprises a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS-CoV-2 antigen; and a trimerization domain, wherein the administering is to a mucosal epithelium.

[00191] Disclosed are methods of treating a subject exposed to SARS-CoV-2 or at risk of being exposed to SARS-CoV-2 comprising administering to a subject an effective amount of a composition comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS-CoV-2 antigen; and a trimerization domain, wherein the administering is to a mucosal epithelium. A subject at risk of being exposed to SARS-CoV-2 can be a first responder, a healthcare worker, a teacher, or anyone knowingly or unknowingly coming in contact with a person infected with SARS-CoV-2. In some aspects, treating a subject at risk of being exposed to SARS-CoV-2 can result in preventing SARS-CoV-2 infection. In some aspects, treating a subject at risk of being exposed to SARS-CoV-2 can result in preventing serious symptoms or side-effects of a SARS-CoV-2 infection, such as but not limited to, pneumonia, organ failure, cytokine storm, or death.

[00192] Disclosed are methods of reducing SARS-CoV-2 viral titers in a subject infected with SARS-CoV-2 comprising administering to a subject an effective amount of a composition comprising any of the peptides, peptide complexes, nucleic acids or vectors disclosed herein. Disclosed are methods of reducing SARS-CoV-2 viral titers in a subject infected with SARS- CoV-2 comprising administering to a subject an effective amount of a composition comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS-CoV-2 antigen; and a trimerization domain, wherein the administering is to a mucosal epithelium.

[00193] Disclosed are methods of treating a subject at risk for infection with coronavirus comprising administering an effective amount of a composition comprising any of the peptides, peptide complexes, nucleic acids or vectors disclosed herein.

[00194] Disclosed are methods of preventing the spread of coronavirus from a subject infected with a coronavirus to a non-infected subject comprising administering an effective amount of a composition comprising any of the peptides, peptide complexes, nucleic acids or vectors disclosed herein.

[00195] Disclosed are methods of preventing coronavirus infection in a subject comprising: administering an effective amount of a composition comprising any of the peptides, peptide complexes, nucleic acids or vectors disclosed herein.

[00196] Disclosed herein are methods of reducing coronavirus copy number per cell comprising administering an effective amount of a composition comprising any of the peptides, peptide complexes, nucleic acids or vectors disclosed herein.

[00197] In some instances, the mucosal epithelium is selected from the group consisting of: lungs, intestines, trachea, colon, nasal tissue, and vaginal tissue. In some aspects, administering is to a mucosal epithelium is a direct or indirect administration of the disclosed peptides, peptide complexes, nucleic acid sequences or vectors to one or more of the mucosal epithelium described herein.

[00198] In some instances, administering is intranasal administering. In some instances, any form of administering that allows for delivery to a mucosal epithelium can be used.

[00199] In some instances, an adjuvant is further administered with the composition. In some instances, an adjuvant can be formulated with the peptide into the disclosed compositions. In some instances, the disclosed compositions or peptides can further comprise an adjuvant. Thus, the adjuvant can be administered simultaneously with the peptide. In some instances, the adjuvant is separate from the disclosed compositions and therefore can be administered simultaneously with the composition or separate from the composition. The adjuvant can be, for example, but is not limited to, CpG, MPL, poly[di(sodium carboxyl atoethylphenoxyjphosphazene I (PCEP), poly[di(sodium carboxyl atophenoxyjphosphazene I (PCPP), the Cholera Toxin-Derived CTA1-DD, Flagellin, IDR1002, a-Galactosylceramide, or saponins. The term “adjuvant” is intended to include any substance which is incorporated into or administered simultaneously with the peptides of the invention and which nonspecifically potentiates the immune response in the subject. Adjuvants include aluminum compounds, e.g., gels, aluminum hydroxide and aluminum phosphate, and Freund's complete or incomplete adjuvant (in which the fusion protein is incorporated in the aqueous phase of a stabilized water in paraffin oil emulsion). The paraffin oil may be replaced with different types of oils, e.g., squalene or peanut oil. Other materials with adjuvant properties include, flagellin, BCG (attenuated Mycobacterium tuberculosis), calcium phosphate, levamisole, isoprinosine, polyanions (e.g., poly A:U) leutinan, pertussis toxin, cholera toxin, lipid A, saponins and peptides, e.g. muramyl dipeptide, dimethyl dioctadecyl-ammonium bromide (DDA); monophosphoryl lipid A (MPL); LTK63, lipophilic quaternary ammonium salt-DDA, Trehalose dimycolate and synthetic derivatives, DDA-MPL, DDA-TDM, DDA-TDB, IC-31, aluminum salts, aluminum hydroxyide, aluminum phosphate, potassium aluminum phosphate, Montanide ISA-51, ISA-720, microparticles, immunostimulatory complexes, liposomes, virosomes, virus-like particles, CpG oligonucleotides, cholera toxin, heat-labile toxin from E. coli, lipoproteins, dendritic cells, IL-12, GM-CSF, nanoparticles including calcium phosphate nanoparticles, combination of soybean oil, emulsifying agents, and ethanol to form a nanoemulsion; AS04, ZADAXIN, or combinations thereof. Rare earth salts, e.g., lanthanum and cerium, may also be used as adjuvants. The amount of adjuvants depends on the subject and the particular peptide used and can be readily determined by one skilled in the art without undue experimentation.

[00200] In some aspects, eliciting a protective immune response comprises eliciting neutralizing antibodies. In some aspects, eliciting a protective immune response comprises activating T cells and B cells. In some aspects, the activated T cells and B cells provide a cellular and humoral response, respectively.

[00201] In some aspects, an effective amount is that amount of the disclosed peptides, peptide complexes or compositions that will alone, or together with further doses, stimulate an immune response as desired. This may involve the stimulation of a humoral antibody response resulting in an increase in antibody titer in serum, improved mucosal immunity, a clonal expansion of cytotoxic T lymphocytes or tolerance to an antigen, including a self-antigen. It is believed that doses ranging from 1 nanogram/kilogram to 100 milligrams/kilogram, depending upon the mode of administration, will be effective. In some aspects, the preferred range is believed to be between about 500 nanograms and 500 micrograms/kilogram, and most preferably between 1 microgram and 100 micrograms/kilogram. The absolute amount will depend upon a variety of factors, including the peptide, peptide complex, or composition selected, the immune modulation desired, whether the administration is in a single or multiple doses, and individual patient parameters including age, physical condition, size and weight. These factors are well known to those of ordinary skill in the art and can be addressed with no more than routine experimentation.

H. Combination Therapy

[00202] Any of the disclosed methods described herein can be performed in combination with one or more of the known standards of care for coronavirus infection. Thus, in some aspects, the methods comprising administering one or more of the disclosed peptide complexes, peptides, compositions or nucleic acids can be combined with an antibody, or antibody cocktail, nanobody, antiviral small molecules, macromolecules of sulfated polysaccharides, and polypeptides. Frequent targets are the viral spike protein, the host angiotensin converting enzyme 2, the host transmembrane protease serine 2, and clathrin-mediated endocytosis. For example, disclosed methods of using TTFields can be performed in combination with one or more of remdesivir (Veklury), Nafamostat, Avigan (favilavir), bamlanivimab, Olumiant and Baricinix (baricitinib), hydroxy chloroquine/chloroquine, Casirivimab and imdevimab (formerly REGN-COV2), PTC299, Leronlimab (PRO 140), Bamlanivimab (LY-CoV555), Lenzilumab, Ivermectin, RLF-100 (aviptadil), Metformin (Glucophage, Glumetza, Riomet), AT-527,

Actemra (tocilizumab), Niclocide (niclosamide), Convalescent plasma, Pepcid (famotidine), Kaletra (lopinavir-ritonavir), Remicade (infliximab), AZD7442, AZD7442, CT-P59, Heparin (UF and LMW), VIR-7831 (GSK4182136), JS016, Kevzara (sarilumab), SACCOVID (CD24Fc), Humira (adalimumab), COVI-GUARD (STI-1499), Dexamethasone (Dextenza, Ozurdex, others), PB1046, Galidesivir, Bucillamine, PF-00835321 (PF-07304814), Eliquis (Apixaban), Takhzyro (lanadelumab), Hydrocortisone, Ilaris (canakinumab), Colchicine (Mitigare, Colcrys), BLD-2660, Avigan (favilavir/avifavir), Rhu-pGSN (gelsolin), MK-4482, TXA127, LAM-002A (apilimod dimesylate), DNL758 (SAR443122), INOpulse, ABX464, AdMSCs, Losmapimod, Mavrilimumab, or Calquence (acalabrutinib), quinoline-based antimalarials ((hydroxy )-chloroquine and others), RAAS modifiers (captopril, losartan, and others), statins (atorvastatin and simvastatin), guanidino-based serine protease inhibitors (camostat and nafamostat), antibacterials (macrolides, clindamycin, and doxycycline), antiparasitics (ivermectin and niclosamide), cardiovascular drugs (amiodarone, verapamil, and tranexamic acid), antipsychotics (chlorpromazine), antivirals (umifenovir and oseltamivir), DPP- 4 inhibitors (linagliptin), JAK inhibitors (baricitinib and others), sulfated glycosaminoglycans (UFH and LMWHs) and polypeptides such as the enzymes DAS181 and rhACE2. They also include the viral spike protein-targeting monoclonal antibodies REGN10933 and REGN10987. [00203] In some aspects, the additional therapeutic agents are selected based on the disease or symptom to be treated. A description of the various classes of suitable pharmacological agents and drugs may be found in Goodman and Gilman, The Pharmacological Basis of Therapeutics, (11th Ed., McGraw-Hill Publishing Co.) (2005). In some aspects, an additional therapeutic agent can be CpG which helps overcome any possible immune tolerance. In some aspects, an additional therapeutic agent can be an anti-viral or any known SARS-CoV-2 therapeutic.

[00204] In some aspects, an additional therapeutic agent can be MPL (Monophosphoryl Lipid A) or C-di-GMP (Cyclic diguanylate monophosphate, CpG). In some aspects, an additional therapeutic agent can be a toll-like receptor (TLR) agonist, which represent different adjuvants, CpG and MPL are examples.

[00205] In some aspects, supplementary immune potentiating agents, such as cytokines, can be delivered in conjunction with the disclosed peptide complexes, peptides and nucleic acids of the invention. The cytokines contemplated are those that will enhance the beneficial effects that result from administering the peptide complexes, peptides and nucleic acids according to the invention. Cytokines are factors that support the growth and maturation of cells, including lymphocytes. It is believed that the addition of cytokines will augment cytokine activity stimulated in vivo by carrying out the methods of the invention. The preferred cytokines are interleukin (IL)-l, IL-2, gamma-interferon and tumor necrosis factor a. Other useful cytokines are believed to be IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, erythropoietin, leukemia inhibitory factor, oncostatin-M, ciliary neurotrophic factor, growth hormone, prolactin, CD40-ligand, CD27-ligand, CD30-ligand, alpha-interferon, beta-interferon, and tumor necrosis factor b. Other cytokines known to modulate T-cell activity in a manner likely to be useful according to the invention are colony stimulating factors and growth factors including granulocyte and/or macrophage stimulating factors (GM-CSF, G-CSF and CSF-1) and platelet derived, epidermal, insulin-like, transforming and fibroblast growth factors. The selection of the particular cytokines will depend upon the particular modulation of the immune system that is desired. The activity of cytokines on particular cell types is known to those of ordinary skill in the art.

I. Kits

[00206] The compositions and materials described above as well as other materials can be packaged together in any suitable combination as a kit useful for performing, or aiding in the performance of, the disclosed method. It is useful if the kit components in a given kit are designed and adapted for use together in the disclosed method. For example disclosed are kits for producing the disclosed peptides, the kit comprising monomeric Fc fragment of an immunoglobulin recognized by a.FcRn and a SARS-CoV-2 antigen. The kits also can contain vectors.

Examples

[00207] FcRn mediates the transfer of IgG across polarized respiratory epithelial cells and prolongs IgG half-life. Described herein is the use of the FcRn to deliver SARS-CoV-2 spike antigens to induce protective immunity against SARS-CoV-2 virus infection. Intranasal immunization (i.n.) with the trimeric spike proteins that target to FcRn plus a mucosal adjuvant conferred significant protection against lethal virus challenge in human ACE2 transgenic mice. The results demonstrate that FcRn can effectively deliver trimeric spike antigens in the respiratory tract and elicit potent protection against lethal SARS-CoV-2 infection. Therefore, FcRn-mediated respiratory immunization can efficiently induce protective respiratory immunity to SARS-COV-2 infection and COVID-19 disease (Figure 1).

1. Importance of developing a nasal spray vaccine against SARS-CoV-2 infection and transmission

[00208] Currently, nucleic acid-, viral vector-, and subunit-based vaccines, are in progress or on the market. However, there is still a need to develop a COVID-19 vaccine inducing a high degree of mucosal immunity to block viral spread. The strategy disclosed herein is based on the following: 1) By exploiting a natural IgG transfer pathway, we proved the concept that FcRn- targeted intranasal immunization of mice with trimeric influenza HA-Fc protein induced both local and systemic immune responses and protected mice from infection. We reason that FcRn mucosal delivery could also enhance mucosal uptake of Fc-fused SARS-CoV-2 S antigens through intranasal delivery. After epithelial transport, S antigens efficiently bind to Fey receptors on dendritic cells. 2). The property of FcRn in protecting IgG from degradation could similarly extend the half-life of S-Fc antigens. This would allow professional antigen presenting cells (APCs), dendritic cell, macrophages, and B cells to sample and present S antigens for a long time in APCs that enhance T cell activation. 3). The full-length proteins S, SI, or RBD in SARS-CoV-2 have been proposed as major vaccine antigens because they induce neutralizing antibodies that prevent host cell attachment and infection by virus. 4). We have produced a trimeric form of SARS-CoV-2 S-Fc, Sl-Fc, RBD-Fc antigens, the mice intranasally immunized with trimeric S-Fc, Sl-Fc or RBD-Fc antigens developed specific neutralizing antibodies. 5). FcRn-mediated IgG transport is well-conserved across species, human FcRn is expected to transport SARS-CoV-2 antigens in humans. 2. Developing an effective mucosal vaccine against SARS-CoV-2.

[00209] SARS-CoV-2 seems more contagious for quickly and easily spreading among people. The virus can spread via droplets or aerosol from the infected individuals with or without symptoms. Given the main cause of patient death is pneumonia, therefore achieving an effective and long-lasting immunity in the respiratory tract would better prevent or control the SARS-CoV-2 spread and infection in the community. However, to elicit resident memory T and B cells in the lung, vaccine antigens must be delivered into the lungs. It has been shown that FcRn mucosal delivery can induce potent protection from influenza infection. FcRn can similarly deliver SARS-CoV-2 S antigens across the respiratory barrier, thus inducing protective respiratory immunity to SARS-CoV-2 viruses. It is expected that mucosal immunity can prevent nasal infection or shedding of the virus. FcRn-targeted delivery represents an important path for developing a mucosal vaccine against SARS-CoV-2.

3. Developing a safe SARS-CoV-2 mucosal vaccine in the young or elderly population. [00210] Elderly people are most likely to develop severe forms of COVID-19, however, achieving immune protection by a vaccine may be challenging in the elderly. Also, although infected children have less symptoms, the immunization of the young population would reduce viral transmission. Since vaccine preparation mainly contains Spike proteins, FcRn mucosal delivery would mitigate the risk and develop an effective and safe immunity in both young and elderly. Overall, FcRn-targeted mucosal vaccination can help control the COVID-19 pandemic but not only preventing the disease severity in individuals, but also stopping viral infection and spread among people.

4. Expression of SARS-COV-2 S, SI, or RBD antigen that is fused to human IgG 1 Fc. [00211] The rationale for using human IgGl is consistent with the fact that it has the highest affinity for activating FcyRI, but the lowest affinity for inhibitory FcyRIIB. Because IgG Fc normally forms a disulfide-bonded dimer, a monomeric Fc was created by substituting cysteines 226 and 229 of human IgGl with serine to eliminate the disulfide bonds. In IgG Fc, the complement Clq-binding motif was eliminated (K322A) (Fig. 2), allowing production of a non- lytic vaccine antigen.

[00212] The entire amino acid (aa) sequence of the SARS-COV-2 was retrieved from Genbank (MN908947). the S gene of SARS-COV-2. The S gene was cloned into eukaryotic expression plasmid pcDNA3 to generate the envelope recombinant plasmids pcDNA3-S (Fig 2). During SARS-COV-2 infection, the S precursor is cleaved into SI and S2. To produce a non- cleavable S protein, mutagenesis was performed at the cleavage site (R685A/R816A) of the S gene to keep the S protein in pre-cleavage conformation. The maintenance of a native conformational structure of SARS-COV-2 Spike antigen in a prefusion state would be critical for maximizing the immunogenicity induced by intranasal vaccination. To maintain the S protein in a prefusion state, two mutations (K986P and V987P) were introduced.

[00213] The SARS-CoV-2 S protein naturally exists as a trimer. To facilitate the trimerization of S protein, a foldon domain from T4 bacteriophage fibritin protein was engineered to the C- terminus of S (residues 15-1214), SI (residues 15-672), and RBD (residues 319-540) genes. As described above, the monomeric human IgGl Fc/wt was fused in frame with the S-foldon, Sl- foldon, and RBD-foldon, generating S-Fc ((Figure 2, construct #1), Sl-Fc (construct #2) and RBD-Fc (construct #3), respectively. In a Coomassie blue staining, the S, S-Fc, Sl-Fc, and RBD-Fc proteins were secreted from 293T or CHO cells (Figure 3). In a Western blot, the secreted S-Fc/wt, Sl-Fc/wt, RBD-Fc/wt proteins were monomers under non-reducing conditions. This confirmed that removal of the disulfide bonds eliminated Fc dimerization. To determine whether S-Fc protein binds to FcRn, it was tested whether S-Fc interacts with Protein A because of the IgG Fc binding sites for both FcRn and Protein A overlap. The S-Fc interacted with Protein A strongly indicating that S-Fc proteins maintain the structure required to interact with FcRn.

5. Intranasal immunization of mouse with S-Fc, Sl-Fc or RBD-Fc induced S-specific antibody immune responses.

[00214] Whether mice intranasally (i.n.) immunized with IgG Fc-fused SI and RBD proteins can develop antibody immune responses was tested. CpG1826 was co-administrated to overcome possible mucosal tolerance. Briefly, mice were i.n. immunized with 10 pg of affinity- purified Sl-Fc, RBD-Fc protein, or PBS in combination with 10 pg CpG, and boosted 2 weeks later with the same dose. Significantly higher titers of total IgG in sera, measured by ELISA, were detected in the Sl-Fc or RBD-Fc immunized mice when compared with PBS-immunized mice (Fig. 4, left panel).

[00215] SARS-CoV-2 neutralization was measured using SARS-CoV-2-FBLuc in a singlecycle pseudovirus neutralization assay in ACE2/293T cells. Pseudovirions were produced by cotransfection Lenti-X 293T cells with pMLV-gag-pol, pFBluc, and pcDNA 3.1 SARS-CoV-2 S (BEI Resources) using Lipofectamine 3000. The supernatant was harvested at 72 hr after transfection. For the neutralization assay, 50 pi of SARS-CoV-2 S pseudovirions was preincubated with an equal volume of medium, containing serum at varying dilutions at room temperature for 1 hour; then, virus-antibody mixtures were added to ACE2/293T cells. Cells were lysed 72 hour later, and luciferase activity was measured using luciferin-containing substrate. The average percent inhibitions by mouse intranasal vaccination are shown in Fig. 4 (right panel). Control sera (control) did not neutralize SARS-CoV-2 in this assay. Sera generated by SI and RBD showed 50 to 60% virus neutralization after vaccination.

[00216] Whether FcRn-dependent respiratory transport augments the immune responses of S antigen was also tested. Wild-type mice (N=6) or FcRn knockout mice (KO) (N=5) were intranasally (i.n.) immunized with 10 pg of S-Fc, or PBS in combination with 10 pg CpG, and boosted 2 weeks later with the same dose. Significantly higher titers of S-specific IgG in sera were seen in the S-Fc immunized mice when compared with that of S-Fc-immunized FcRn KO mice or PBS-treated groups of mice 2 weeks after the boost (Fig. 5, Left). Moreover, sera from the S-Fc/wt immunized mice exhibited strong neutralizing activity relative to FcRn KO or PBS control groups (Fig. 5, Right). Overall, the data indicate that Fc-fused S, SI or RBD antigens administered via the intranasal route can induce the S-specific neutralizing antibody, this immune response should depend on FcRn transport.

6. FcRn-targeted nasal vaccination leads to increased protection against lethal SARS-

CoV-2 infection.

[00217] SARS-CoV-2 virus infects human ACE2 transgenic mice. To test whether the immune responses elicited by FcRn-targeted intranasal vaccination provide protection, 8-10- week-old human ACE2 transgenic mice were i.n. immunized intranasally (i.n.) with 10 pg of S- Fc, or PBS in combination with 10 pg CpG, and boosted 2 weeks later with the same dose. The mice were challenged i.n. with a lethal dose (2.5xl0 ⁴ TCID50) of SARS-CoV-2 virus two weeks after the boost in BSL-3 facility. Mice were monitored and weighed daily for a 14-day period and were euthanized after 25% body weight loss as endpoint. All mice in the PBS groups had weight loss (up to 25%) within 8 days after the challenge and either succumbed to infection or euthanized. In contrast, all the S-Fc-immunized mice had no body-weight loss (Fig. 6, Left). Hence, the trimeric S-Fc protein-immunized mice led to a full protection (Fig. 6, right). Also, virus replicating was assessed in different tissues by 5 days after challenge (Fig. 7). Virus was not detected in tissues, including lung, of trimeric S-Fc-immunized mice. However, different titers of virus were detected in the nasal turbinate, lung, and brain of the PBS group (Fig. 7), indicating these control mice failed to contain viral replication. To further confirm the protection, histopathology was performed and the extent of lung inflammation was detemined. The mouse lungs in PBS control mice showed remarkable infiltration of monocytes and lymphocytes after challenge, resulting in high levels of inflammation (Fig. 8, right). In contrast, mice immunized with the trimeric S-Fc/wt protein had significantly lower lung inflammation scores (Fig. 8, middle), which was comparable to the lung structure of uninfected mouse (Fig. 8, left). Overall, the findings show that FcRn- mediated intranasal delivery of the trimeric S-Fc/wt conferred significant protection against lethal SARS-CoV-2 virus challenge, resulting in decreased mortality, viral replication, and pulmonary inflammation.

[00218] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the method and compositions described herein. Such equivalents are intended to be encompassed by the following claims.