Title:
RECOMBINANT PARAINFLUENZA VIRUS VACCINES ATTENUATED BY DELETION OR ABLATION OF THE C, D OR V GENES
Document Type and Number:
WIPO Patent Application WO2001003744
Kind Code:
A3
Abstract:
Recombinant parainfluenza virus (PIV) are provided in which expression of the C, D and/or V translational open reading frame(s) (ORFs) is reduced or ablated to yield novel PIV vaccine candidates. Expression of the C, D and/or V ORF(s) is reduced or ablated by modifying a recombinant PIV genome or antigenome, for example by introduction of a stop codon, by a mutation in an RNA editing site, by a mutation that alters the amino acid specified by an initiation codon, or by a frame shift mutation in the targeted ORF(s). Alternatively, the C, D and/or V ORF(s) is deleted in whole or in part to render the protein(s) encoded thereby partially or entirely non-functional or to disrupt protein expression altogether. C, D and/or V ORF(s) deletion and knock out mutants possess highly desirable phenotypic characteristics for vaccine development. These deletion and knock out mutations changes specify one or more desired phenotypic changes in the resulting virus or subviral particle. Vaccine candidates are generated that show a change in viral growth characteristics, attenuation, plaque size, and/or a change in cytopathogenicity, among other novel phenotypes. A variety of additional mutations and nucleotide modifications are provided within the C, D and/or V ORF(s) deletion or ablation mutant PIV of the invention to yield desired phenotypic and structural effects.
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Inventors:
DURBIN ANNA P (US)
COLLINS PETER L (US)
MURPHY BRIAN R (US)
COLLINS PETER L (US)
MURPHY BRIAN R (US)
Application Number:
PCT/US2000/018523
Publication Date:
September 13, 2001
Filing Date:
July 06, 2000
Export Citation:
Assignee:
US GOV HEALTH & HUMAN SERV (US)
DURBIN ANNA P (US)
COLLINS PETER L (US)
MURPHY BRIAN R (US)
DURBIN ANNA P (US)
COLLINS PETER L (US)
MURPHY BRIAN R (US)
International Classes:
C12N15/09; A61K9/12; A61K39/102; A61K48/00; A61P31/16; C07K14/115; C12N7/00; C12N7/04; A61K39/00; (IPC1-7): C12N15/45; C07K14/115; C12N7/04; A61K39/155; C12N15/11
Domestic Patent References:
| WO1998013501A2 | 1998-04-02 |
Other References:
SKIADOPOULOS, M.A. ET AL.: "Identification of mutations contributing to the temperature-sensitive, cold-adapted and attenuation phenotypes of the live-attenuated cold-passage 45 (cp45) human Parainfluenza virus 3 candidate vaccine", JOURNAL OF VIROLOGY, vol. 73, no. 2, February 1999 (1999-02-01), pages 1374 - 1381, XP000943239
KUROTANI, A. ET AL.: "Sendai virus C proteins are categorically nonessential gene products but silencing their expression severely impairs viral replication and pathogenesis", GENES TO CELLS, vol. 3, 1998, pages 111 - 124, XP000943648
LATORRE, P. ET AL.: "The various Sendai virus C proteins are not functionally equivalent and exert both positive and negative effects on viral RNA accumulation during the course of infection", JOURNAL OF VIROLOGY, vol. 72, no. 7, July 1998 (1998-07-01), pages 5984 - 5993, XP000943630
GARCIN, D. ET AL.: "A point mutation in the Sendai virus accessory C proteins attenuates virulence for mice, but not virus growth in cell culture", VIROLOGY, vol. 238, 1997, pages 424 - 431, XP000941491
RADECKE, F. ET AL.: "The nonstructural C protein is not essential for multiplication of Edmonston B strain measles virus in cultured cells", VIROLOGY, vol. 217, 1996, pages 418 - 421, XP002154434
ESCOFFIER, C. ET AL.: "Nonstructural C protein is required for efficient measles virus replication in human peripheral blood cells", JOURNAL OF VIROLOGY, vol. 73, no. 2, February 1999 (1999-02-01), pages 1695 - 1698, XP000943627
VALSAMAKIS, A. ET AL.: "Recombinant measles viruses with mutations in the C, V, or F gene have altered growth phenotypes in vivo", JOURNAL OF VIROLOGY, vol. 72, no. 10, October 1998 (1998-10-01), pages 7754 - 7761, XP000943629
DURBIN, A.P. ET AL.: "Mutations in the C, D, and V open reading frames of human Parainfluenza virus type 3 attenuate replication in rodents and primates", VIROLOGY, vol. 261, September 1999 (1999-09-01), pages 319 - 330, XP000941468
DELENDA C ET AL: "NORMAL CELLULAR REPLICATION OF SENDAI VIRUS WITHOUT THE TRANS-FRAME, NONSTRUCTURAL V PROTEIN", VIROLOGY,ACADEMIC PRESS,ORLANDO,US, vol. 228, 1997, pages 55 - 62, XP000941489, ISSN: 0042-6822
KATO A ET AL: "THE PARAMYXOVIRUS, SENDAI VIRUS, V PROTEIN ENCODES A LUXURY FUNCTION REQUIRED FOR VIRAL PATHOGENESIS", EMBO JOURNAL,OXFORD UNIVERSITY PRESS, SURREY,GB, vol. 16, 1997, pages 578 - 587, XP000941467, ISSN: 0261-4189
SCHNEIDER H ET AL: "RECOMBINANT MEASLES VIRUSES DEFECTIVE FOR RNA EDITING AND V PROTEIN SYNTHESIS ARE VIABLE IN CULTURED CELLS", VIROLOGY,ACADEMIC PRESS,ORLANDO,US, vol. 227, 1997, pages 314 - 322, XP000941469, ISSN: 0042-6822
PELET, T. ET AL.: "The P gene of bovine parainfluenza virus 3 expresses all three reading frames from a single mRNA editing site", THE EMBO JOURNAL, vol. 10, no. 2, 1991, pages 443 - 448, XP000942201
GALINSKI, M. ET AL.: "RNA editing in the phosphoprotein gene of the human parainfluenza virus type 3", VIROLOGY, vol. 186, 1992, pages 543 - 550, XP000942200
KUROTANI, A. ET AL.: "Sendai virus C proteins are categorically nonessential gene products but silencing their expression severely impairs viral replication and pathogenesis", GENES TO CELLS, vol. 3, 1998, pages 111 - 124, XP000943648
LATORRE, P. ET AL.: "The various Sendai virus C proteins are not functionally equivalent and exert both positive and negative effects on viral RNA accumulation during the course of infection", JOURNAL OF VIROLOGY, vol. 72, no. 7, July 1998 (1998-07-01), pages 5984 - 5993, XP000943630
GARCIN, D. ET AL.: "A point mutation in the Sendai virus accessory C proteins attenuates virulence for mice, but not virus growth in cell culture", VIROLOGY, vol. 238, 1997, pages 424 - 431, XP000941491
RADECKE, F. ET AL.: "The nonstructural C protein is not essential for multiplication of Edmonston B strain measles virus in cultured cells", VIROLOGY, vol. 217, 1996, pages 418 - 421, XP002154434
ESCOFFIER, C. ET AL.: "Nonstructural C protein is required for efficient measles virus replication in human peripheral blood cells", JOURNAL OF VIROLOGY, vol. 73, no. 2, February 1999 (1999-02-01), pages 1695 - 1698, XP000943627
VALSAMAKIS, A. ET AL.: "Recombinant measles viruses with mutations in the C, V, or F gene have altered growth phenotypes in vivo", JOURNAL OF VIROLOGY, vol. 72, no. 10, October 1998 (1998-10-01), pages 7754 - 7761, XP000943629
DURBIN, A.P. ET AL.: "Mutations in the C, D, and V open reading frames of human Parainfluenza virus type 3 attenuate replication in rodents and primates", VIROLOGY, vol. 261, September 1999 (1999-09-01), pages 319 - 330, XP000941468
DELENDA C ET AL: "NORMAL CELLULAR REPLICATION OF SENDAI VIRUS WITHOUT THE TRANS-FRAME, NONSTRUCTURAL V PROTEIN", VIROLOGY,ACADEMIC PRESS,ORLANDO,US, vol. 228, 1997, pages 55 - 62, XP000941489, ISSN: 0042-6822
KATO A ET AL: "THE PARAMYXOVIRUS, SENDAI VIRUS, V PROTEIN ENCODES A LUXURY FUNCTION REQUIRED FOR VIRAL PATHOGENESIS", EMBO JOURNAL,OXFORD UNIVERSITY PRESS, SURREY,GB, vol. 16, 1997, pages 578 - 587, XP000941467, ISSN: 0261-4189
SCHNEIDER H ET AL: "RECOMBINANT MEASLES VIRUSES DEFECTIVE FOR RNA EDITING AND V PROTEIN SYNTHESIS ARE VIABLE IN CULTURED CELLS", VIROLOGY,ACADEMIC PRESS,ORLANDO,US, vol. 227, 1997, pages 314 - 322, XP000941469, ISSN: 0042-6822
PELET, T. ET AL.: "The P gene of bovine parainfluenza virus 3 expresses all three reading frames from a single mRNA editing site", THE EMBO JOURNAL, vol. 10, no. 2, 1991, pages 443 - 448, XP000942201
GALINSKI, M. ET AL.: "RNA editing in the phosphoprotein gene of the human parainfluenza virus type 3", VIROLOGY, vol. 186, 1992, pages 543 - 550, XP000942200
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