The Frequency of Vaccine-Induced T-Cell Responses Does Not Predict the Rate of Acquisition after Repeated Intrarectal SIVmac239 Challenges in Mamu-B*08 + Rhesus Macaques

Author:

Martins Mauricio A.1ORCID,Gonzalez-Nieto Lucas1,Shin Young C.1,Domingues Aline1,Gutman Martin J.1,Maxwell Helen S.1,Magnani Diogo M.1,Ricciardi Michael J.1,Pedreño-Lopez Núria1,Bailey Varian K.1,Altman John D.2,Parks Christopher L.3,Allison David B.4,Ejima Keisuke4,Rakasz Eva G.5,Capuano Saverio5,Desrosiers Ronald C.1ORCID,Lifson Jeffrey D.6,Watkins David I.1

Affiliation:

1. Department of Pathology, University of Miami, Miami, Florida, USA

2. Department of Microbiology and Immunology, Emory University, Atlanta, Georgia, USA

3. International AIDS Vaccine Initiative, AIDS Vaccine Design and Development Laboratory, Brooklyn, New York, USA

4. School of Public Health, Indiana University—Bloomington, Bloomington, Indiana, USA

5. Wisconsin National Primate Research Center, University of Wisconsin—Madison, Madison, Wisconsin, USA

6. AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA

Abstract

It is generally accepted that the antiviral effects of vaccine-induced classical CD8 + T-cell responses against human immunodeficiency virus (HIV) are limited to partial reductions in viremia after the establishment of productive infection. Here we show that rhesus macaques (RMs) vaccinated with Vif and Nef acquired simian immunodeficiency virus (SIV) infection at a lower (albeit not statistically significant) rate than control RMs following repeated intrarectal challenges with a pathogenic SIV clone. All animals in the present experiment expressed the elite control-associated major histocompatibility complex class I (MHC-I) molecule Mamu-B*08 that binds immunodominant epitopes in Vif and Nef. Though preliminary, these results provide tantalizing evidence that the protective efficacy of vaccine-elicited CD8 + T cells may be greater than previously thought. Future studies should examine if vaccine-induced cellular immunity can prevent systemic viral replication in RMs that do not express MHC-I alleles associated with elite control of SIV infection.

Funder

HHS | NIH | National Cancer Institute

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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