A Phase 1 Study Evaluating the Safety, Tolerability, and Immunogenicity of V4020 Vaccine in Healthy Volunteers

The V4020 vaccine was prepared using an iDNA® infectious clone that encodes the full-length rearranged genomic RNA downstream from the optimized CMV promoter. Compared to the wild type VEEV, V4020 contains genetic rearrangement within the genomic RNA, with the capsid gene placed downstream from the glycoprotein genes. V4020 also includes attenuating mutations from the VEE TC83 vaccine, nucleotide A at position 3 in the untranslated region and E2-120Arg in the E2 glycoprotein. Notably, the E2-120Arg attenuating mutation was genetically engineered in V4020 to prevent reversion mutations. The E2-120Arg was encoded in V4020 by a CGA codon instead of AGA in the TC83 virus. Therefore, in the V4020 vaccine, at least two mutations would be needed to revert to the wildtype ACA (E2-120Thr). In contrast, in the TC83 vaccine, an AGA codon encodes the attenuating mutation E2-120Arg, and a single point mutation would be sufficient to revert to the 213 VEEV wild type ACA (E2-120Thr).