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Protection of Hamsters by Venezuelan Equine Encephalitis Virus Candidate Vaccine V3526 against Lethal Challenge by Mosquito Bite and Intraperitoneal Injection

In an attempt to improve the current live, attenuated vaccine (TC-83) for Venezuelan equine encephalitis virus (VEEV), specific mutations associated with attenuation of VEEV in rodent models were inserted into a full-length cDNA clone of the Trinidad donkey strain of VEEV by site-directed mutagenesis. Because some viruses have been reported to be more pathogenic when introduced by mosquito bite than the same virus introduced by needle inoculation, there were concerns that the presence of mosquito saliva, or changes in the virus caused by replication in a mosquito, might allow the virus to overcome the protective effects of prior vaccination with V3526. Therefore, we determined if hamsters vaccinated with V3526 were protected from challenge with the virulent Trinidad donkey strain of VEEV. All non-vaccinated hamsters died after intraperitoneal challenge or after being fed on by VEEV-inoculated Aedes taeniorhynchus. In contrast, hamsters vaccinated with V3526 were resistant to intraperitoneal challenge and infection by VEEV-infected Ae. taeniorhynchus. Therefore, the V3526 candidate vaccine elicits protection against VEEV infection by mosquito bite.

Received December 28, 2006. Accepted for publication October 13, 2007.

Acknowledgments: We thank D. Kline (Medical and Veterinary Entomology Research Laboratory) for providing the MAVERL strain of Ae. taeniorhynchus; U. Gastelum, R. Kopka, D. Price, and D. Nash for their assistance in rearing the mosquitoes; D. Dohm for his assistance in processing specimens; and M. O’Guinn, S. Goodwin, and K. Kenyon for their critical reading of the manuscript.

Disclaimer: Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army.

^* Address correspondence to Michael J. Turell, Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702-5011. E-mail: michael.turell{at}amedd.army.mil

Authors’ address: Michael J. Turell and Michael D. Parker, Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702-5011, Telephone: 301-619-4921, Fax: 301-619-2290, E-mails: michael.turell{at}amedd.army.mil and michael.parker{at}amedd.army.mil.