Correlates of Protection Against SIVmac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors
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 SI...
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doaj-cba17e029b06400699766f31d61b895c2020-11-25T01:54:27ZengElsevierEBioMedicine2352-39642018-05-01312535Correlates of Protection Against SIVmac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus VectorsSteven Tuyishime0Larissa H. Haut1Raj K. Kurupati2James M. Billingsley3Diane Carnathan4Sailaja Gangahara5Tiffany M. Styles6ZhiQuan Xiang7Yan Li8Malte Zopfs9Qin Liu10XiangYang Zhou11Mark G. Lewis12Rama R. Amara13Steven Bosinger14Guido Silvestri15Hildegund C.J. Ertl16Wistar Institute, Philadelphia, PA, United States; Gene Therapy and Vaccines Graduate Group of the University of PA, Philadelphia, PA, United StatesWistar Institute, Philadelphia, PA, United StatesWistar Institute, Philadelphia, PA, United StatesEmory University and Yerkes National Primate Center, Atlanta, GA, United StatesEmory University and Yerkes National Primate Center, Atlanta, GA, United StatesEmory University and Yerkes National Primate Center, Atlanta, GA, United StatesEmory University and Yerkes National Primate Center, Atlanta, GA, United StatesWistar Institute, Philadelphia, PA, United StatesWistar Institute, Philadelphia, PA, United StatesHarvard University, Cambridge, MA, United StatesWistar Institute, Philadelphia, PA, United StatesWistar Institute, Philadelphia, PA, United StatesBioqual Inc., Rockville, MD, United StatesEmory University and Yerkes National Primate Center, Atlanta, GA, United StatesEmory University and Yerkes National Primate Center, Atlanta, GA, United StatesEmory University and Yerkes National Primate Center, Atlanta, GA, United StatesWistar Institute, Philadelphia, PA, United States; Corresponding author at: Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104, USA.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 profileshttp://www.sciencedirect.com/science/article/pii/S2352396418300847 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Correlates of Protection Against SIVmac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors EBioMedicine |
author_facet |
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 |
author_sort |
Steven Tuyishime |
title |
Correlates of Protection Against SIVmac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors |
title_short |
Correlates of Protection Against SIVmac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors |
title_full |
Correlates of Protection Against SIVmac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors |
title_fullStr |
Correlates of Protection Against SIVmac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors |
title_full_unstemmed |
Correlates of Protection Against SIVmac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors |
title_sort |
correlates of protection against sivmac251 infection in rhesus macaques immunized with chimpanzee-derived adenovirus vectors |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2018-05-01 |
description |
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 |
url |
http://www.sciencedirect.com/science/article/pii/S2352396418300847 |
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