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Effect of Antigen, Type I IFN and STING Signaling on CD8 T Cell Immunity With Adenoviral Vaccines

ABSTRACT: Recombinant adenoviral vectors (rAds), derived from distinct species with different serotypes, are lead vaccine candidates against Ebola, HIV, Tuberculosis and Malaria based on their potent induction of T cell immunity in humans. Importantly, rAds vary in their ability to induce protective cellular immunity. Here, the in vivo mechanisms controlling potency of CD8 T cell responses were assessed after vaccination with human-, chimpanzee- and simian-derived rAds encoding SIV-Gag. After rAd vaccination, we quantified antigen (Ag) expression and performed expression profiling of innate immune response genes in the draining lymph node. The most potent rAds (human-derived rAd5 and chimpanzee-derived chAd3) induced high and persistent Ag expression with low innate gene activation, while the less potent rAds exhibited reduced Ag expression with robust innate gene activation associated primarily with interferon (IFN) signaling. Abrogation of type I IFN or stimulator of IFN genes (STING) signaling increased Ag expression and accelerated CD8 T cell response kinetics, but did not alter memory responses or protection. Thus, the magnitude of memory CD8 T cell immune responses induced by rAds correlates with Ag expression but is independent of IFN and STING. These findings provide criteria for optimal induction of protective CD8 T cell immunity with rAd vaccines.

ORGANISM(S): Mus musculus

PROVIDER: GSE64548 | GEO | 2014/12/30

SECONDARY ACCESSION(S): PRJNA271285

REPOSITORIES: GEO

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