Correlates of Protection Against SIVmac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors

• Main Authors: Steven Tuyishime, Larissa H. Haut, Raj K. Kurupati, James M. Billingsley, Diane Carnathan, Sailaja Gangahara, Tiffany M. Styles, ZhiQuan Xiang, Yan Li, Malte Zopfs, Qin Liu, XiangYang Zhou, Mark G. Lewis, Rama R. Amara, Steven Bosinger, Guido Silvestri, Hildegund C.J. Ertl
• Format: Article
• Language: English
• Published: Elsevier 2018-05-01
• Series: EBioMedicine
• Online Access: http://www.sciencedirect.com/science/article/pii/S2352396418300847

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 SIVmac251. 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 (TFH) cell responses and highly activated CD8+ T cells may play a role in protection. Keywords: HIV-1 vaccine, Adenovirus vector, Mucosal challenge, Protection, Gene expression profiles