Construction & Evaluation of a Polyvalent Genetically Engineered Vaccine Candidate for VEE
Abstract
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 C57B1/6 mice. One of these mutants induced complete protection in C57B1/6 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 C57B1/6 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 27, 1994
- Accession Number
- ADA285754
Entities
People
- Nancy L. Davis
- Robert E. Johnston
Organizations
- University of North Carolina at Chapel Hill