Protection of Hamsters by Venezuelan Equine Encephalitis Virus Candidate Vaccine V3526 Against Lethal Challenge by Mosquito Bite and Intraperitoneal Injection
Abstract
In an attempt to improve upon the current live, attenuated vaccine (TC-83) for Venezuelan equine encephalitis virus (VEEV), the V3526 vaccine candidate strain of VEEV was prepared by site-directed mutagenesis. Because studies indicate that virus introduced by mosquito bite may be more pathogenic than the same virus introduced by needle inoculation, there were concerns that the presence of mosquito saliva, or changes in the virus due to 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 virulent Trinidad donkey strain of VEEV. All non-vaccinated hamsters succumbed after intraperitoneal challenge or after being fed on by VEEV-inoculated Ochlerotatus taeniorhynchus. In contrast, hamsters vaccinated with V3526 were resistant to intraperitoneal challenge and infection by VEEV-infected Oc. taeniorhynchus. Therefore, the V3526 candidate vaccine elicits protection against VEEV infection by mosquito bite. In efforts to develop an improved live-attenuated vaccine for Venezuelan equine encephalitis virus (VEEV), specific mutations associated with attenuation of VEEV in rodent models were identified and inserted into a full-length cDNA clone of VEEV to produce selected isogenic strains containing one or more attenuating mutations. These were evaluated for their potential as a live, attenuated VEEV vaccine, and the V3526 strain, containing a deletion of the furin cleavage site in PE2 as well as a suppressor mutation in E1, was shown to protect mice, hamsters, and nonhuman primates challenged either by intraperitoneal (I.P.) inoculation or by aerosol. In addition, this strain replicates less efficiently in potential mosquito vectors and does not revert to virulence after multiple passages in mosquitoes. In nature, most infections are caused by the bite of an infective mosquito.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2008
- Accession Number
- ADA478656
Entities
People
- Michael D. Parker
- Michael J. Turell
Organizations
- United States Army Medical Research Institute of Infectious Diseases