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

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

Author information

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 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:

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

PMID:
29685793
PMCID:
PMC6013748
DOI:
10.1016/j.ebiom.2018.02.025
[Indexed for MEDLINE]
Free PMC Article

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