Evaluation of Biological and cDNA Clone-Derived Stocks of Venezuelan Equine Encephalitis Virus TC-83 Vaccine Strain

Abstract

The objective of this research study was to evaluate the potential antibody escape mutations identified. The specific aims of this study were as follows: Aim 1: Generate mutant virus stocks containing the identified mutations, singly or in combination; Aim 2: Characterize the mutant viruses, along with the biological or clone-derived wild-type viruses, for fitness and ability to bind antibody 1A3B-7. The results of these studies demonstrated that the biological and clone-derived VEEV TC-83 viruses behaved similarly with regards to replication in cell culture and antibody neutralization. Though there appeared to be some differences in virulence in the C3H/HeN mouse model, the difference in survival was not statistically different. The results of these studies were important to provide the necessary foundation for characterization of the potential antibody escape mutations as the mutants viruses must be clone-derived from cDNA. Future research will observe the two escape mutant viruses with nucleotide changes in the E2 glycoprotein at nucleotide 9177 and 9189. Evaluation of the escape mutants may suggest the most effective way to develop a therapeutic against VEEV would be through the administration of a broadly neutralizing antibody or a cocktail of monoclonal antibodies which recognize multiple epitopes on the surface of the virus particle.