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

• Published in: EBioMedicine 2018-05, Vol.31, p.25-35
• Main Authors: Tuyishime, Steven, Haut, Larissa H., Kurupati, Raj K., Billingsley, James M., Carnathan, Diane, Gangahara, Sailaja, Styles, Tiffany M., Xiang, ZhiQuan, Li, Yan, Zopfs, Malte, Liu, Qin, Zhou, XiangYang, Lewis, Mark G., Amara, Rama R., Bosinger, Steven, Silvestri, Guido, Ertl, Hildegund C.J.
• Format: Article
• Language: English
• Subjects: Adenovirus vector; Gene expression profiles; HIV-1 vaccine; Mucosal challenge; Protection; Research Paper
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2018.02.025

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. •Adenovirus vaccines for protect against SIV infection•Env-specific antibodies affect SIV acquisition•Protective T cells have unique transcriptional profiles HIV-1 remains endemic claiming on average the lives of >1 million individual each year. An efficacious vaccine would be highly desirable to stop further spread of HIV-1. We conducted pre-clinical studies in monkeys with two chimpanzee-derived adenovirus vectors expressing antigens of SIV, a virus that is used for pre-clinical AIDS vaccine studies. Vaccinated monkeys had lower viral burden upon SIV infection and showed accelerated clearance of the virus. Correlates of protection were identified through biological studies and by analyzing the gene expression profiles of circulating lymphocyte subsets.