Evaluation of formalin inactivated V3526 virus with adjuvant as a next generation vaccine candidate for Venezuelan equine encephalitis virus

Abstract

V3526, a genetically modified strain of Venezuelan equine encephalitis virus (VEEV), was formalin inactivated for evaluation as a next generation vaccine candidate for VEEV. In this study, we tested formalin-inactivated V3526 (fV3526) with and without adjuvant for immunogenicity and efficacy in BALB/c mice and results were compared to the existing inactivated VEEV vaccine, C84. Mice were vaccinated intramuscularly (IM) or subcutaneously (SC) with fV3526 formulations and challenged with VEEV IAB Trinidad donkey (VEEV TrD) strain by SC or aerosol exposure. Efficacy following SC or aerosol challenge was not significantly different between the fV3526 formulations or compared to C84 despite C84 being administered in more doses and higher concentration of viral protein per dose. These data support further evaluation of fV3526 formulations as a next generation VEEV vaccine.

Figure 1

Virus-binding antibody responses induced to VEEV TrD virus by vaccination with fV3526 formulated with the indicated adjuvant and C84. Sera were obtained from mice on Day 49 post-primary vaccination. These data are reported as the geometric mean endpoint titers as determined by ELISA. Black bars: IM vaccinated, Gray bars: SC vaccinated. C84 administered IM was not evaluated. *statistically different from fV3526/CpG administered IM (p<0.05) **statistically different from all other groups (p<0.01). The titers presented are combined titers from similarly vaccinated mice (same route, same formulation) giving a total of 20 mice per group. Groups were later split into 10 mice challenged by the aerosol route and 10 challenged by the SC route.

Figure 2

Neutralizing antibody responses induced to VEEV TrD virus by vaccinations with fV3526 formulated with the indicated adjuvant and C84. Sera were obtained from mice on Day 49 post-primary vaccination. These data are reported as the geometric mean endpoint titers that inhibited plaque formation by 80%. Black bars: IM vaccinated, Gray bars: SC vaccinated. C84 administered IM was not evaluated. * statistically different from fV3526/Alhydrogel™ administered IM (p<0.05). ** statistically different from C84 (p<0.05). The titers presented are combined titers from similarly vaccinated mice (same route, same formulation) giving a total of 20 mice per group. Groups were later split into 10 mice challenged by the aerosol route and 10 challenged by the SC route.

Figure 3

Average survival among fV3526+CpG and fV3526+CpG+Alhydrogel™ vaccinated mice following aerosol challenge. Data represent 2 vaccination/challenge iterations for fV3526+CpG and 3 vaccination/challenge iterations for fV3526+CpG+Alhydrogel™. Each iteration consisted of 10 mice/group and a group of 10 sham-vaccinated. All mice were challenged by the aerosol route.