Construction & Evaluation of a Polyvalent Genetically Engineered Vaccine Candidate for VEE
Annual rept. 1 Jul 1993-30 Jun 1994
NORTH CAROLINA UNIV AT CHAPEL HILL
Pagination or Media Count:
We have constructed a full-length cDNA clone of the virulent Trinidad Donkey strain of Venezuelan equine encephalitis virus, from which infectious RNA genomes can be transcribed in vitro, as the basis for development of a recombinant five attenuated vaccine strain for VEE. We are using recombinant DNA techniques to produce a low reversion five virus vaccine by combining multiple independently attenuating mutations in a single virus genome. Four triple mutants were avirulent in both CD-1 and C57B16 mice. One of these mutants induced complete protection in C57B16 mice against intraperitoneal ip. or aerosol challenge with the virulent parent virus, while all four mutants induced complete protection in CD-1 mice against ip. challenge. PE2 cleavage defective mutants were avirulent in C57B16 mice inoculated subcutaneously sc. and in CD-1 mice inoculated sc., intracranially or intranasally in., and produced a solid immunity to ip. or in. challenge CD-1 mice. The growth of these mutants is restricted in cultured mosquito cells. Collaborators at USAMRIID are testing the most promising attenuated in monkeys. VEE Attenuating Mutations, Attenuated Triple Mutants of VEE, Protection of Rodents Against Virulent Virus Challenge, BD, BL3, Vaccines Biotechnology, RAD IV.