Transmission Potential of Two Chimeric Western Equine Encephalitis Vaccine Candidates in Culex tarsalis

Joan L. Kenney Department of Pathology, Department of Microbiology and Immunology, Sealy Center for Vaccine Development, Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

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A. Paige Adams Department of Pathology, Department of Microbiology and Immunology, Sealy Center for Vaccine Development, Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

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Scott C. Weaver Department of Pathology, Department of Microbiology and Immunology, Sealy Center for Vaccine Development, Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

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Western equine encephalitis virus (WEEV) is a zoonotic alphavirus that circulates in western North America between passerine birds and mosquitoes, primarily Culex tarsalis. 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 Cx. tarsalis 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, Cx. tarsalis, and are unlikely to be reintroduced into a natural WEEV transmission cycle.

Author Notes

*Address correspondence to Joan L. Kenney, Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, 2.144 Keiller Building, Galveston, TX 77555-0428. E-mail: jlkenney@utmb.edu

Financial support: This study was supported by a grant from the National Institute of Allergy and Infectious Disease through the Western Regional Center of Excellence for Biodefense and Emerging Infectious Disease Research, National Institutes of Health (NIH) grant U54 AIO57156. Joan L. Kenney was supported by a Centers for Disease Control and Prevention fellowship for training in vector-borne infectious diseases (TO1/CCT622892) and by the NIH-sponsored Emerging Infectious Diseases Training Program (T32-AI07536). A. Paige Adams was supported by the James W. McLaughlin Fellowship Fund.

Authors' addresses: Joan L. Kenney, A. Paige Adams, and Scott C. Weaver, Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0428, E-mails: jlkenney@utmb.edu, apadams@utmb.edu, and sweaver@utmb.edu.

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