Induction of robust cytotoxic T lymphocytes using adenovirus-vectored multivalent antigen cocktail

Abstract

Abstract Development of subunit vaccines against complex pathogens entails inclusion of multiple targets to improve efficacy and or broaden protection. Importantly, testing of an immunogen in the actual host that require protection can hasten vaccine development and generate knowledge needed to generate other similar vaccines. The African Swine Fever Virus (ASFV) causes a fatal hemorrhagic disease in domestic swine and, at present, no treatment or vaccine is available. Previous studies suggest that induction of ASFV-specific cytotoxic T lymphocytes (CTLs) is critical for protection. We evaluated immunogenicity of adenovirus-vectored ASFV multivalent cocktail formulated in two adjuvants and at two doses in swine. The immunogen induced unprecedented CTL responses against all the antigens in the cocktail. Notably, CTL responses were detected in swine immunized with a low dose (1 × 1010 ifu/each construct) and a high dose (1 × 1011 ifu/each construct). In addition, both adjuvants elicited strong CTL responses. Significant antigen-specific IFN-γ+ responses were detected in PBMCs of vaccinees post-priming and post-boosting. Furthermore, the cocktail induced robust antigen-specific antibody responses against all the antigens and the antibody responses underwent rapid isotype-switching within one week post-priming. The primed antibody responses underwent rapid recall upon boost four months post-priming. Taken together, this study showed for the first time that the adenovirus-vectored ASFV multivalent cocktail safely induced robust cellular and antibody responses in swine following homologous prime-boost immunization. The relevance of the induced immune responses in regards to protection will be evaluated in a challenge study.