Centers for Disease Control and Prevention, 2009. West Nile Virus - Statistics, Surveillance, and Control - Case Count 2008. Available at: http://www.cdc.gov/ncidod/dvbid/westnile/surv&controlCaseCount08_detailed.htm. Accessed May 20, 2009.
Davis BS, Chang GJJ, Cropp B, Roehrig JT, Martin DA, Mitchell CJ, Bowen R, Bunning ML, 2001. West Nile virus recombinant DNA vaccine protects mouse and horse from virus challenge and expresses in vitro a noninfectious recombinant antigen that can be used in enzyme-linked immunosorbent assays. J Virol 75: 4040ā4047.
Ng T, Hathaway D, Jennings N, Champ D, Chiang YW, Chu HJ, 2003. Equine vaccine for West Nile virus. Dev Biol (Basel) 114: 221ā227.
Minke JM, Siger L, Karaca K, Austgen L, Gordy P, Bowen R, Renshaw RW, Loosmore S, Audonnet JC, Nordgren B, 2004. Recombinant canarypoxvirus vaccine carrying the prM/E genes of West Nile virus protects horses against a West Nile virus-mosquito challenge. Arch Virol Suppl: 221ā230.
Martin JE, Pierson TC, Hubka S, Rucker S, Gordon IJ, Enama ME, Andrews CA, Xu Q, Davis BS, Nason M, Fay M, Koup RA, Roederer M, Bailer RT, Gomez PL, Mascola JR, Chang GJ, Nabel GJ, Graham BS, 2007. A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial. J Infect Dis 196: 1732ā1740.
Monath TP, Liu J, Kanesa-Thasan N, Myers GA, Nichols R, Deary A, McCarthy K, Johnson C, Ermak T, Shin S, Arroyo J, Guirakhoo F, Kennedy JS, Ennis FA, Green S, Bedford P, 2006. A live, attenuated recombinant West Nile virus vaccine. Proc Natl Acad Sci USA 103: 6694ā6699.
Watts DM, Tesh RB, Siirin M, Rosa AT, Newman PC, Clements DE, Ogata S, Coller BA, Weeks-Levy C, Lieberman MM, 2007. Efficacy and durability of a recombinant subunit West Nile vaccine candidate in protecting hamsters from West Nile encephalitis. Vaccine 25: 2913ā2918.
Konishi E, Mason PW, 1993. Proper maturation of the Japanese encephalitis virus envelope glycoprotein requires cosynthesis with the premembrane protein. J Virol 67: 1672ā1675.
Mason PW, Pincus S, Fournier MJ, Mason TL, Shope RE, Paoletti E, 1991. Japanese encephalitis virus-vaccinia recombinants produce particulate forms of the structural membrane proteins and induce high levels of protection against lethal JEV infection. Virology 180: 294ā305.
Konishi E, Pincus S, Paoletti E, Shope RE, Burrage T, Mason PW, 1992. Mice immunized with a subviral particle containing the Japanese encephalitis virus prM/M and E proteins are protected from lethal JEV infection. Virology 188: 714ā720.
Qiao M, Ashok M, Bernard KA, Palacios G, Zhou ZH, Lipkin WI, Liang TJ, 2004. Induction of sterilizing immunity against West Nile Virus (WNV), by immunization with WNV-like particles produced in insect cells. J Infect Dis 190: 2104ā2108.
Aberle JH, Aberle SW, Allison SL, Stiasny K, Ecker M, Mandl CW, Berger R, Heinz FX, 1999. A DNA immunization model study with constructs expressing the tick-borne encephalitis virus envelope protein E in different physical forms. J Immunol 163: 6756ā6761.
Konishi E, Yamaoka M, Kurane I, Mason PW, 2000. A DNA vaccine expressing dengue type 2 virus premembrane and envelope genes induces neutralizing antibody and memory B cells in mice. Vaccine 18: 1133ā1139.
Mason PW, Shustov AV, Frolov I, 2006. Production and characterization of vaccines based on flaviviruses defective in replication. Virology 351: 432ā443.
Widman DG, Ishikawa T, Fayzulin R, Bourne N, Mason PW, 2008. Construction and characterization of a second-generation pseudoinfectious West Nile virus vaccine propagated using a new cultivation system. Vaccine 26: 2762ā2771.
Widman DG, Ishikawa T, Winkelmann ER, Infante E, Bourne N, Mason PW, 2009. RepliVAX WN, a single-cycle flavivirus vaccine to prevent West Nile disease, elicits durable protective immunity in hamsters. Vaccine 27: 5550ā5553.
Hoke CH, Nisalak A, Sangawhipa N, Jatanasen S, Laorakapongse T, Innis BL, Kotchasenee S, Gingrich JB, Latendresse J, Fukai K, 1988. Protection against Japanese encephalitis by inactivated vaccines. N Engl J Med 319: 608ā614.
Halstead SB, Tsai TF, 2004. Japanese encephalitis vaccine. Plotkin S, Orenstein WA, eds. Vaccine. Philadelphia: W.B. Saunders Company, 919ā957.
World Health Organization, 1998. Japanese encephalitis vaccines. Wkly Epidemiol Rec 73: 337ā344.
Xiao SY, Guzman H, Zhang H, Travassos da Rosa AP, Tesh RB, 2001. West Nile virus infection in the golden hamster (Mesocricetus auratus): a model for West Nile encephalitis. Emerg Infect Dis 7: 714ā721.
Bourne N, Scholle F, Silva MC, Rossi SL, Dewsbury N, Judy B, De Aguiar JB, Leon MA, Estes DM, Fayzulin R, Mason PW, 2007. Early production of type i interferon during West Nile virus infection: role for lymphoid tissues in IRF3-independent interferon production. J Virol 81: 9100ā9108.
Monath TP, Levenbook I, Soike K, Zhang ZX, Ratterree M, Draper K, Barrett ADT, Nichols R, Weltzin R, Arroyo J, Guirakhoo F, 2000. Chimeric yellow fever virus 17D-Japanese encephalitis virus vaccine: dose-response effectiveness and extended safety testing in rhesus monkeys. J Virol 74: 1742ā1751.
Clarke DH, Casals J, 1958. Techniques for hemagglutination and hemagglutination-inhibition with arthropod-borne viruses. Am J Trop Med Hyg 7: 561ā573.
Caul EO, Smyth GW, Clarke SK, 1974. A simplified method for the detection of rubella-specific IgM employing sucrose density fractionation and 2-mercaptoethanol. J Hyg (Lond) 73: 329ā340.
Ratterree MS, Gutierrez RA, Travassos da Rosa AP, Dille BJ, Beasley DW, Bohm RP, Desai SM, Didier PJ, Bikenmeyer LG, Dawson GJ, Leary TP, Schochetman G, Phillippi-Falkenstein K, Arroyo J, Barrett AD, Tesh RB, 2004. Experimental infection of rhesus macaques with West Nile virus: level and duration of viremia and kinetics of the antibody response after infection. J Infect Dis 189: 669ā676.
Arroyo J, Miller C, Catalan J, Myers GA, Ratterree MS, Trent DW, Monath TP, 2004. ChimeriVax-West Nile virus live-attenuated vaccine: preclinical evaluation of safety, immunogenicity, and efficacy. J Virol 78: 12497ā12507.
Pletnev AG, Swayne DE, Speicher J, Rumyantsev AA, Murphy BR, 2006. Chimeric West Nile/dengue virus vaccine candidate: preclinical evaluation in mice, geese and monkeys for safety and immunogenicity. Vaccine 24: 6392ā6404.
Shrestha B, Ng T, Chu HJ, Noll M, Diamond MS, 2008. The relative contribution of antibody and CD8+ T cells to vaccine immunity against West Nile encephalitis virus. Vaccine 26: 2020ā2033.
Beasley DW, Li L, Suderman MT, Guirakhoo F, Trent DW, Monath TP, Shope RE, Barrett AD, 2004. Protection against Japanese encephalitis virus strains representing four genotypes by passive transfer of sera raised against ChimeriVax-JE experimental vaccine. Vaccine 22: 3722ā3726.
Shrestha B, Diamond MS, 2004. Role of CD8+ T cells in control of West Nile virus infection. J Virol 78: 8312ā8321.
Kreil TR, Maier E, Fraiss S, Eibl MM, 1998. Neutralizing antibodies protect against lethal flavivirus challenge but allow for the development of active humoral immunity to a nonstructural virus protein. J Virol 72: 3076ā3081.
Barrett PN, Schober-Bendixen S, Ehrlich HJ, 2003. History of TBE vaccines. Vaccine 21 (Suppl 1): S41āS49.
Monath TP, Nichols R, Archambault WT, Moore L, Marchesani R, Tian J, Shope RE, Thomas N, Schrader R, Furby D, Bedford P, 2002. Comparative safety and immunogenicity of two yellow fever 17D vaccines (ARILVAX and YF-VAX) in a phase III multicenter, double-blind clinical trial. Am J Trop Med Hyg 66: 533ā541.
Pletnev AG, Claire MS, Elkins R, Speicher J, Murphy BR, Chanock RM, 2003. Molecularly engineered live-attenuated chimeric West Nile/dengue virus vaccines protect rhesus monkeys from West Nile virus. Virology 314: 190ā195.
Silva MC, Guerrero-Plata A, Gilfoy FD, Garofalo RP, Mason PW, 2007. Differential activation of human monocyte-derived and plasmacytoid dendritic cells by West Nile virus generated in different host cells. J Virol 81: 13640ā13648.
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West Nile virus (WNV) causes serious neurologic disease, but no licensed vaccines are available to prevent this disease in humans. We have developed RepliVAX WN, a single-cycle flavivirus with an expected safety profile superior to other types of live-attenuated viral vaccines. In this report we describe studies examining RepliVAX WN safety, potency, and efficacy in a non-human primate model of WNV infection. A single immunization of four rhesus macaques with RepliVAX WN was safe and elicited detectable neutralizing antibody titers and IgM and IgG responses, and IgG titers were increased in two animals that received a second immunization. After challenge with WNV, three of four immunized animals were completely protected from viremia, and the remaining animal showed minimal viremia on one day. In contrast, the unvaccinated animal developed viremia that lasted six days. These results demonstrate the efficacy and safety of RepliVAX WN in this primate model of WNV infection.
Disclosure: P. Mason is an inventor on the patents filed for RepliVAX technology. This statement is made in the interest of full disclosure and not because the author considers this a conflict of interest.
Financial support: This study was supported by a grant from the National Institute of Allergy and Infectious Diseases to Peter W. Mason and the Nonhuman Primate Core through the Western Regional Center of Excellence for Biodefense and Emerging Infectious Disease Research (National Institutes of Health [NIH] grant U54 AI057156). Douglas G. Widman was supported by a James W. McLaughlin fellowship. Amelia P. Travassos Da Rosa and Robert B. Tesh were supported in part by NIH contract NO1-AI30027. Luis D. Giavedoni and Vida L. Hodara were supported by NIH grants R51 RR13566 and R24 RR023345.
Authors' addresses: Douglas G. Widman, Department of Microbiology and Immunology, 3.218 Mary Moody Northen Pavilion, University of Texas Medical Branch, Galveston, TX (current address: Lineberger Comprehensive Cancer Center; University of North Carolina, CB7295, Chapel Hill, NC, E-mail: dgwidman@med.unc.edu). Tomohiro Ishikawa, Department of Microbiology and Immunology, 3.218 Mary Moody Northen Pavilion, University of Texas Medical Branch, Galveston, TX (current address: Department of International Health, Kobe University Graduate School of Health Sciences, Kobe, Japan, E-mail: toishika@port.kobe-u.ac.jp). Luis D. Giavedoni, Vida L. Hodara, Jean L. Patterson, and Ricardo Carrion Jr, Southwest National Primate Research Center and Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX, E-mails: lgiavedo@sfbr.org, vhodara@sfbr.org, jpatterson@sfbr.org, and carrion@sfbr.org. Melissa de la Garza, Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, TX, E-mail: mdelagar@sfbr.org. Jessica A. Montalbo, Veterinary Food Analysis and Diagnostic Laboratory, Department of Defense, Fort Sam Houston, TX, E-mail: jessica.montalbo@us.army.mil. Amelia P. Travassos Da Rosa, Department of Pathology, 4.104 Keiller Building, University of Texas Medical Branch, Galveston, TX, E-mail: aptravas@utmb.edu. Robert B. Tesh, Department of Microbiology and Immunology, and Department of Pathology, 3.146 Keiller Building, University of Texas Medical Branch, Galveston, TX, E-mail: rtesh@utmb.edu. Nigel Bourne, Departments of Microbiology and Immunology, Pathology, Pediatrics, and Sealy Center for Vaccine Development, 3.206C Mary Moody Northen Pavilion, University of Texas Medical Branch, Galveston, TX, E-mail: nibourne@utmb.edu. Peter W. Mason, Department of Microbiology and Immunology, and Department of Pathology, 3.206B Mary Moody Northen Pavilion, University of Texas Medical Branch, Galveston, TX, E-mail: pwmason@utmb.edu (current address: Microbial Molecular Biology, Novartis Vaccines and Diagnostics, Cambridge, MA, E-mail: peter.mason@novartis.com).
Centers for Disease Control and Prevention, 2009. West Nile Virus - Statistics, Surveillance, and Control - Case Count 2008. Available at: http://www.cdc.gov/ncidod/dvbid/westnile/surv&controlCaseCount08_detailed.htm. Accessed May 20, 2009.
Davis BS, Chang GJJ, Cropp B, Roehrig JT, Martin DA, Mitchell CJ, Bowen R, Bunning ML, 2001. West Nile virus recombinant DNA vaccine protects mouse and horse from virus challenge and expresses in vitro a noninfectious recombinant antigen that can be used in enzyme-linked immunosorbent assays. J Virol 75: 4040ā4047.
Ng T, Hathaway D, Jennings N, Champ D, Chiang YW, Chu HJ, 2003. Equine vaccine for West Nile virus. Dev Biol (Basel) 114: 221ā227.
Minke JM, Siger L, Karaca K, Austgen L, Gordy P, Bowen R, Renshaw RW, Loosmore S, Audonnet JC, Nordgren B, 2004. Recombinant canarypoxvirus vaccine carrying the prM/E genes of West Nile virus protects horses against a West Nile virus-mosquito challenge. Arch Virol Suppl: 221ā230.
Martin JE, Pierson TC, Hubka S, Rucker S, Gordon IJ, Enama ME, Andrews CA, Xu Q, Davis BS, Nason M, Fay M, Koup RA, Roederer M, Bailer RT, Gomez PL, Mascola JR, Chang GJ, Nabel GJ, Graham BS, 2007. A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial. J Infect Dis 196: 1732ā1740.
Monath TP, Liu J, Kanesa-Thasan N, Myers GA, Nichols R, Deary A, McCarthy K, Johnson C, Ermak T, Shin S, Arroyo J, Guirakhoo F, Kennedy JS, Ennis FA, Green S, Bedford P, 2006. A live, attenuated recombinant West Nile virus vaccine. Proc Natl Acad Sci USA 103: 6694ā6699.
Watts DM, Tesh RB, Siirin M, Rosa AT, Newman PC, Clements DE, Ogata S, Coller BA, Weeks-Levy C, Lieberman MM, 2007. Efficacy and durability of a recombinant subunit West Nile vaccine candidate in protecting hamsters from West Nile encephalitis. Vaccine 25: 2913ā2918.
Konishi E, Mason PW, 1993. Proper maturation of the Japanese encephalitis virus envelope glycoprotein requires cosynthesis with the premembrane protein. J Virol 67: 1672ā1675.
Mason PW, Pincus S, Fournier MJ, Mason TL, Shope RE, Paoletti E, 1991. Japanese encephalitis virus-vaccinia recombinants produce particulate forms of the structural membrane proteins and induce high levels of protection against lethal JEV infection. Virology 180: 294ā305.
Konishi E, Pincus S, Paoletti E, Shope RE, Burrage T, Mason PW, 1992. Mice immunized with a subviral particle containing the Japanese encephalitis virus prM/M and E proteins are protected from lethal JEV infection. Virology 188: 714ā720.
Qiao M, Ashok M, Bernard KA, Palacios G, Zhou ZH, Lipkin WI, Liang TJ, 2004. Induction of sterilizing immunity against West Nile Virus (WNV), by immunization with WNV-like particles produced in insect cells. J Infect Dis 190: 2104ā2108.
Aberle JH, Aberle SW, Allison SL, Stiasny K, Ecker M, Mandl CW, Berger R, Heinz FX, 1999. A DNA immunization model study with constructs expressing the tick-borne encephalitis virus envelope protein E in different physical forms. J Immunol 163: 6756ā6761.
Konishi E, Yamaoka M, Kurane I, Mason PW, 2000. A DNA vaccine expressing dengue type 2 virus premembrane and envelope genes induces neutralizing antibody and memory B cells in mice. Vaccine 18: 1133ā1139.
Mason PW, Shustov AV, Frolov I, 2006. Production and characterization of vaccines based on flaviviruses defective in replication. Virology 351: 432ā443.
Widman DG, Ishikawa T, Fayzulin R, Bourne N, Mason PW, 2008. Construction and characterization of a second-generation pseudoinfectious West Nile virus vaccine propagated using a new cultivation system. Vaccine 26: 2762ā2771.
Widman DG, Ishikawa T, Winkelmann ER, Infante E, Bourne N, Mason PW, 2009. RepliVAX WN, a single-cycle flavivirus vaccine to prevent West Nile disease, elicits durable protective immunity in hamsters. Vaccine 27: 5550ā5553.
Hoke CH, Nisalak A, Sangawhipa N, Jatanasen S, Laorakapongse T, Innis BL, Kotchasenee S, Gingrich JB, Latendresse J, Fukai K, 1988. Protection against Japanese encephalitis by inactivated vaccines. N Engl J Med 319: 608ā614.
Halstead SB, Tsai TF, 2004. Japanese encephalitis vaccine. Plotkin S, Orenstein WA, eds. Vaccine. Philadelphia: W.B. Saunders Company, 919ā957.
World Health Organization, 1998. Japanese encephalitis vaccines. Wkly Epidemiol Rec 73: 337ā344.
Xiao SY, Guzman H, Zhang H, Travassos da Rosa AP, Tesh RB, 2001. West Nile virus infection in the golden hamster (Mesocricetus auratus): a model for West Nile encephalitis. Emerg Infect Dis 7: 714ā721.
Bourne N, Scholle F, Silva MC, Rossi SL, Dewsbury N, Judy B, De Aguiar JB, Leon MA, Estes DM, Fayzulin R, Mason PW, 2007. Early production of type i interferon during West Nile virus infection: role for lymphoid tissues in IRF3-independent interferon production. J Virol 81: 9100ā9108.
Monath TP, Levenbook I, Soike K, Zhang ZX, Ratterree M, Draper K, Barrett ADT, Nichols R, Weltzin R, Arroyo J, Guirakhoo F, 2000. Chimeric yellow fever virus 17D-Japanese encephalitis virus vaccine: dose-response effectiveness and extended safety testing in rhesus monkeys. J Virol 74: 1742ā1751.
Clarke DH, Casals J, 1958. Techniques for hemagglutination and hemagglutination-inhibition with arthropod-borne viruses. Am J Trop Med Hyg 7: 561ā573.
Caul EO, Smyth GW, Clarke SK, 1974. A simplified method for the detection of rubella-specific IgM employing sucrose density fractionation and 2-mercaptoethanol. J Hyg (Lond) 73: 329ā340.
Ratterree MS, Gutierrez RA, Travassos da Rosa AP, Dille BJ, Beasley DW, Bohm RP, Desai SM, Didier PJ, Bikenmeyer LG, Dawson GJ, Leary TP, Schochetman G, Phillippi-Falkenstein K, Arroyo J, Barrett AD, Tesh RB, 2004. Experimental infection of rhesus macaques with West Nile virus: level and duration of viremia and kinetics of the antibody response after infection. J Infect Dis 189: 669ā676.
Arroyo J, Miller C, Catalan J, Myers GA, Ratterree MS, Trent DW, Monath TP, 2004. ChimeriVax-West Nile virus live-attenuated vaccine: preclinical evaluation of safety, immunogenicity, and efficacy. J Virol 78: 12497ā12507.
Pletnev AG, Swayne DE, Speicher J, Rumyantsev AA, Murphy BR, 2006. Chimeric West Nile/dengue virus vaccine candidate: preclinical evaluation in mice, geese and monkeys for safety and immunogenicity. Vaccine 24: 6392ā6404.
Shrestha B, Ng T, Chu HJ, Noll M, Diamond MS, 2008. The relative contribution of antibody and CD8+ T cells to vaccine immunity against West Nile encephalitis virus. Vaccine 26: 2020ā2033.
Beasley DW, Li L, Suderman MT, Guirakhoo F, Trent DW, Monath TP, Shope RE, Barrett AD, 2004. Protection against Japanese encephalitis virus strains representing four genotypes by passive transfer of sera raised against ChimeriVax-JE experimental vaccine. Vaccine 22: 3722ā3726.
Shrestha B, Diamond MS, 2004. Role of CD8+ T cells in control of West Nile virus infection. J Virol 78: 8312ā8321.
Kreil TR, Maier E, Fraiss S, Eibl MM, 1998. Neutralizing antibodies protect against lethal flavivirus challenge but allow for the development of active humoral immunity to a nonstructural virus protein. J Virol 72: 3076ā3081.
Barrett PN, Schober-Bendixen S, Ehrlich HJ, 2003. History of TBE vaccines. Vaccine 21 (Suppl 1): S41āS49.
Monath TP, Nichols R, Archambault WT, Moore L, Marchesani R, Tian J, Shope RE, Thomas N, Schrader R, Furby D, Bedford P, 2002. Comparative safety and immunogenicity of two yellow fever 17D vaccines (ARILVAX and YF-VAX) in a phase III multicenter, double-blind clinical trial. Am J Trop Med Hyg 66: 533ā541.
Pletnev AG, Claire MS, Elkins R, Speicher J, Murphy BR, Chanock RM, 2003. Molecularly engineered live-attenuated chimeric West Nile/dengue virus vaccines protect rhesus monkeys from West Nile virus. Virology 314: 190ā195.
Silva MC, Guerrero-Plata A, Gilfoy FD, Garofalo RP, Mason PW, 2007. Differential activation of human monocyte-derived and plasmacytoid dendritic cells by West Nile virus generated in different host cells. J Virol 81: 13640ā13648.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 36 | 36 | 10 |
Full Text Views | 286 | 98 | 0 |
PDF Downloads | 60 | 38 | 0 |