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

EBioMedicine (May 2018)

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

Affiliations

Steven Tuyishime: Wistar Institute, Philadelphia, PA, United States; Gene Therapy and Vaccines Graduate Group of the University of PA, Philadelphia, PA, United States
Larissa H. Haut: Wistar Institute, Philadelphia, PA, United States
Raj K. Kurupati: Wistar Institute, Philadelphia, PA, United States
James M. Billingsley: Emory University and Yerkes National Primate Center, Atlanta, GA, United States
Diane Carnathan: Emory University and Yerkes National Primate Center, Atlanta, GA, United States
Sailaja Gangahara: Emory University and Yerkes National Primate Center, Atlanta, GA, United States
Tiffany M. Styles: Emory University and Yerkes National Primate Center, Atlanta, GA, United States
ZhiQuan Xiang: Wistar Institute, Philadelphia, PA, United States
Yan Li: Wistar Institute, Philadelphia, PA, United States
Malte Zopfs: Harvard University, Cambridge, MA, United States
Qin Liu: Wistar Institute, Philadelphia, PA, United States
XiangYang Zhou: Wistar Institute, Philadelphia, PA, United States
Mark G. Lewis: Bioqual Inc., Rockville, MD, United States
Rama R. Amara: Emory University and Yerkes National Primate Center, Atlanta, GA, United States
Steven Bosinger: Emory University and Yerkes National Primate Center, Atlanta, GA, United States
Guido Silvestri: Emory University and Yerkes National Primate Center, Atlanta, GA, United States
Hildegund C.J. Ertl: Wistar Institute, Philadelphia, PA, United States; Corresponding author at: Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104, USA.

Journal volume & issue: Vol. 31
pp. 25 – 35

Abstract

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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

Published in EBioMedicine

ISSN: 2352-3964 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General)
Website: http://www.journals.elsevier.com/ebiomedicine/

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