Volume 82, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Western equine encephalitis virus (WEEV) is a zoonotic alphavirus that circulates in western North America between passerine birds and mosquitoes, primarily . Since it was isolated in 1930, WEEV has caused tens of thousands of equine deaths in addition to thousands of human cases. In addition because WEEV is a virus of agricultural importance in addition to a public health threat, we developed two live-attenuated chimeric vaccine candidates that have been shown to be immunogenic and efficacious in mouse models. Vaccine candidate strains were developed by inserting the structural protein genes of WEEV strain McMillan (McM) or CO92-1356 into a Sindbis virus (SINV) strain AR339 backbone. The SIN/McM chimera also derived the N-terminal half of its capsid gene from a North American eastern equine encephalitis virus (EEEV) strain FL39-939 (henceforth referred to as SIN/EEE/McM). Although these vaccines do not generate viremia in mice, we further assessed their safety by exposing to artificial blood meals containing high viral titers of each vaccine candidate. Both viruses exhibited a decreased rate of infection, dissemination, and transmission potential compared with the parental alphaviruses. Specifically, SIN/CO92 infected 37% of mosquitoes and disseminated in 8%, but failed to reach the saliva of the mosquitoes. In contrast, the SIN/EEE/McM virus was unable to infect, disseminate, or be transmitted in the saliva of any mosquitoes. These findings suggest that both vaccine candidates are less competent than the parental strains to be transmitted by the primary mosquito vector, , and are unlikely to be reintroduced into a natural WEEV transmission cycle.


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  1. Centers for Disease Control and Prevention, 2005. Arboviral Encephalitides. Disease DoV-BI, ed. Fact Sheet: Western Equine Encephalitis. Available at: http://www.cdc.gov/ncidod/dvbid/Arbor/weefact.htm.
  2. Weaver SC, Kang W, Shirako Y, Rumenapf T, Strauss EG, Strauss JH, , 1997. Recombinational history and molecular evolution of western equine encephalomyelitis complex alphaviruses. J Virol 71: 613623.
  3. National Institute of Allergy and Infectious Diseases, 2003. Biodefense Research Agenda for Category B and C Priority Pathogens. Bethesda, MD: NIAID Biodefense Research.
  4. Reisen WK, Monath TP, Monath TP, , 1988. Western equine encephalomyelitis. , ed. Western Equine Encephalomyelitis. Boca Raton, FL: CRC Press, 89137.
  5. Chamberlain RW, , 1962. Vector relationships of the arthropod-borne encephalitides in North America. Ann NY Acad Sci 76: 6181.
  6. Hess A, Hayes R, , 1967. Seasonal dynamics of western encephalitis virus. Am J Med Sci 253: 333348.[Crossref]
  7. Reeves WC, Hammon WM, Longshore WA, Jr McClure HE, Geib AF, , 1962. Epidemiology of the arthropod-borne viral encephalitides in Kern County, California, 1943–1952. Public Health Univ Calif 4: 1257.
  8. Hammon WM, Reeves WC, Gray M, , 1943. Mosquito vectors and inapparent animal reservoirs of St. Louis and western equine encephalitis viruses. Am J Public Health Nations Health 33: 201207.[Crossref]
  9. Jensen T, Washino RK, , 1991. An assessment of the biological capacity of a Sacramento Valley population of Aedes melanimon to vector arboviruses. Am J Trop Med Hyg 44: 355363.
  10. Hardy J, Reeves WC, Bruen JP, Presser SB, , 1979. Vector competence of Culex tarsalis and other mosquito species for western equine encephalomyelitis virus. Arctic Tropical Arboviruses 10: 157171.[Crossref]
  11. Hardy JL, Bruen JP, , 1974. Aedes melanimon as a vector of WEE virus in California. Proceedings of the California Mosquito Control Association 42: 36.
  12. Kramer LD, Reisen WK, Chiles RE, , 1998. Vector competence of Aedes dorsalis (Diptera: Culicidae) from Morro Bay, California, for western equine encephalomyelitis virus. J Med Entomol 35: 10201024.[Crossref]
  13. Reisen WK, Lothrop HD, Chiles RE, , 1998. Ecology of Aedes dorsalis (Diptera: Culicidae) in relation to western equine encephalomyelitis virus in the Coachella Valley of California. J Med Entomol 35: 561566.[Crossref]
  14. Hardy JL, , 1987. The ecology of western equine encephalomyelitis virus in the Central Valley of California, 1945–1985. Am J Trop Med Hyg 37: 18S32S.
  15. Olson JG, Reeves WC, Emmons RW, Milby MM, , 1979. Correlation of Culex tarsalis population indices with the incidence of St. Louis encephalitis and western equine encephalomyelitis in California. Am J Trop Med Hyg 28: 335343.
  16. U.S. Department of Agriculture, 2007. Veterinary Biologic Products. Ames, IA: Center for Veterinary Biologics, U.S. Department of Agriculture.
  17. Atasheva S, Wang E, Adams AP, Plante KS, Ni S, Taylor K, Miller ME, Frolov I, Weaver SC, , 2009. Chimeric alphavirus vaccine candidates protect mice from intranasal challenge with western equine encephalitis virus. Vaccine 27: 43094319.[Crossref]
  18. Aguilar PV, Paessler S, Carrara AS, Baron S, Poast J, Wang E, Moncayo AC, Anishchenko M, Watts D, Tesh RB, Weaver SC, , 2005. Variation in interferon sensitivity and induction among strains of eastern equine encephalitis virus. J Virol 79: 1130011310.[Crossref]
  19. Frolova E, Frolov I, Schlesinger S, , 1997. Packaging signals in alphaviruses. J Virol 71: 248258.
  20. Atasheva S, Wang E, Adams AP, Plant KS, Ni S, Taylor K, Miller ME, Frolov I, Weaver SC, , 2009. Chimeric alphavirus vaccine candidates protect mice from intranasal challenge with western equine encephalitis virus. Vaccine 27: 43094319.[Crossref]
  21. Wang E, Petrakova O, Adams AP, Aguilar PV, Kang W, Paessler S, Volk SM, Frolov I, Weaver SC, , 2007. Chimeric Sindbis/eastern equine encephalitis vaccine candidates are highly attenuated and immunogenic in mice. Vaccine 25: 75737581.[Crossref]
  22. Fine PEM, Carneiro IA, , 1999. Transmissibility and persistence of oral polio vaccine viruses: implications for the Global Poliomyelitis Eradication Initiative. Am J Epidemiol 150: 10011021.[Crossref]
  23. Aguilar PV, Adams AP, Wang E, Kang W, Carrara AS, Anishchenko M, Frolov I, Weaver SC, , 2008. Structural and nonstructural protein genome regions of eastern equine encephalitis virus are determinants of interferon sensitivity and murine virulence. J Virol 82: 49204930.[Crossref]
  24. Gerberg EJ, Barnard DR, Ward RA, , 1994. Manual for Mosquito Rearing and Experimental Techniques. Bulletin No. 5. Lake Charles, LA: American Mosquito Control Association.
  25. Beaty BJ, Calisher CH, Shope RE, Schmidt NJ, Emmons RW, , 1989. Arboviruses. , eds. Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections. Sixth edition. Washington, DC: American Public Health Association, 797855.
  26. Smith DR, Carrara AS, Aguilar PV, Weaver SC, , 2005. Evaluation of methods to assess transmission potential of Venezuelan equine encephalitis virus by mosquitoes and estimation of mosquito saliva titers. Am J Trop Med Hyg 73: 3339.
  27. Waldridge BM, Wenzel JG, Ellis AC, Rowe-Morton SE, Bridges ER, D’Andrea G, Wint R, , 2003. Serologic responses to eastern and western equine encephalomyelitis vaccination in previously vaccinated horses. Vet Ther 4: 242248.
  28. Kramer LD, Hardy JL, Presser SB, Houk EJ, , 1981. Dissemination barriers for western equine encephalomyelitis virus in Culex tarsalis infected after ingestion of low viral doses. Am J Trop Med Hyg 30: 190197.
  29. Vaughan JA, Turell MJ, , 1996. Dual host infections: enhanced infectivity of eastern equine encephalitis virus to Aedes mosquitoes mediated by Brugia microfilariae . Am J Trop Med Hyg 54: 105109.
  30. Meyers WM, Neafie RC, Marty AM, Wear DJ, , (eds.). Pathology of Infectious Diseases, vol 1. Helminthiases. Washington, DC: Armed Forces Institute of Pathology, 245306.
  31. Arrigo NC, Watts DM, Frolov I, Weaver SC, , 2008. Experimental infection of Aedes sollicitans and Aedes taeniorhynchus with two chimeric Sindbis/eastern equine encephalitis virus vaccine candidates. Am J Trop Med Hyg 78: 9397.

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  • Received : 16 Feb 2009
  • Accepted : 25 Oct 2009

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