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

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

doi:10.1016/j.ebiom.2018.02.025

Correlates of Protection Against SIV_mac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors

EBioMedicine. 2018 May:31:25-35. doi: 10.1016/j.ebiom.2018.02.025. Epub 2018 Mar 4.

Authors

Steven Tuyishime¹, Larissa H Haut², Raj K Kurupati², James M Billingsley³, Diane Carnathan³, Sailaja Gangahara³, Tiffany M Styles³, ZhiQuan Xiang², Yan Li², Malte Zopfs⁴, Qin Liu², XiangYang Zhou², Mark G Lewis⁵, Rama R Amara³, Steven Bosinger³, Guido Silvestri³, Hildegund C J Ertl⁶

Affiliations

¹ Wistar Institute, Philadelphia, PA, United States; Gene Therapy and Vaccines Graduate Group of the University of PA, Philadelphia, PA, United States.
² Wistar Institute, Philadelphia, PA, United States.
³ Emory University and Yerkes National Primate Center, Atlanta, GA, United States.
⁴ Harvard University, Cambridge, MA, United States.
⁵ Bioqual Inc., Rockville, MD, United States.
⁶ Wistar Institute, Philadelphia, PA, United States. Electronic address: ertl@wistar.org.

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)_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.

Keywords: Adenovirus vector; Gene expression profiles; HIV-1 vaccine; Mucosal challenge; Protection.

MeSH terms

Adenoviridae / genetics
Adenoviridae / immunology*
Animals
CD4-Positive T-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / pathology
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / pathology
Gene Products, env / genetics
Gene Products, env / immunology*
Genetic Vectors / genetics
Genetic Vectors / immunology*
Immunity, Cellular*
Macaca mulatta
Simian Acquired Immunodeficiency Syndrome / genetics
Simian Acquired Immunodeficiency Syndrome / immunology*
Simian Acquired Immunodeficiency Syndrome / pathology
Simian Acquired Immunodeficiency Syndrome / prevention & control
Simian Immunodeficiency Virus / genetics
Simian Immunodeficiency Virus / immunology*
Vaccination

Substances

Gene Products, env

Grants and funding

P51 OD011132/OD/NIH HHS/United States