Correlates of Protection Against SIV(mac251) Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors

We report on prime-boost vaccine regimens with two simian adenovirus (Ad) vectors (SAdV) or two human serotype Ad vectors (HAdV) expressing Gag and gp160 of simian immunodeficiency virus (SIV)(mac239) tested in HAdV-seropositive rhesus macaques (RMs) repeatedly challenged rectally with low doses of SIV(mac251.) Both vaccine regimens reduced set point and peak viral loads (PVL) and accelerated viral clearance. In SAdV-vaccinated controller genotype RMs resistance against infection correlated with levels of envelope (Env)-specific antibody (Ab) titers. In both vaccine groups CD8(+)T cells controlled viral loads (VL) upon infection. Circulating CD4(+) and CD8(+) T cells showed significant changes in their transcriptome over time following vaccination, which differed between the vaccine groups. T cells from SIV-resistant RMs had unique transcriptional profiles indicating that both follicular T helper (T(FH)) cell responses and highly activated CD8(+) T cells may play a role in protection.