Correlates of Protection Against SIV<sub>mac251</sub> Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors.

Tuyishime, Steven; Haut, Larissa H; Kurupati, Raj K; Billingsley, James M; Carnathan, Diane; Gangahara, Sailaja; Styles, Tiffany M; Xiang, ZhiQuan et al. · EBioMedicine · 2018

basic_science · Level V

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Abstract

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)<sub>mac239</sub> tested in HAdV-seropositive rhesus macaques (RMs) repeatedly challenged rectally with low doses of SIV<sub>mac251.</sub> 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<sup>+</sup>T cells controlled viral loads (VL) upon infection. Circulating CD4<sup>+</sup> and CD8<sup>+</sup> 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<sub>FH</sub>) cell responses and highly activated CD8<sup>+</sup> T cells may play a role in protection.

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