A trivalent alphavirus virus-like replicon particle vaccine induces cell-mediated responses against conserved glycoprotein regions

Abstract

Abstract Venezuelan (VEEV), eastern (EEEV) and western (WEEV) equine encephalitis viruses are highly infectious and neuroinvasive when aerosolized, making them threats for weaponization. In contrast to subcutaneous infection, studies suggest that protection from aerosol challenge is partially cell-mediated, albeit poorly understood. A trivalent (VEEV/EEEV/WEEV) virus-like replicon particle (triVRP) vaccine is protective against aerosol challenge in mice, yet the correlates of protection are unclear. To investigate, mice were vaccinated (day 0 and 28; PBS or triVRP) and spleens were harvested for analysis. Using an ex vivo splenocyte expansion assay with peptides from VEEV, EEEV and WEEV glycoprotein libraries, IFNγ-producing memory CD8+ T cells were identified. T cell-specific epitopes were mapped, and the most immunodominant were found within regions of sequence homology between strains. Thus, ongoing studies evaluate potential monovalent vaccine cross-protection, which would greatly reduce manufacturing costs. Understanding vaccine-induced responses will inform rational design and clinical evaluation.