Mamu-B*17 + Rhesus Macaques Vaccinated with env , vif , and nef Manifest Early Control of SIVmac239 Replication

Author:

Martins Mauricio A.1ORCID,Tully Damien C.2,Pedreño-Lopez Núria1,von Bredow Benjamin3,Pauthner Matthias G.456,Shin Young C.1,Yuan Maoli7,Lima Noemia S.8,Bean David J.2,Gonzalez-Nieto Lucas1,Domingues Aline1,Gutman Martin J.1,Maxwell Helen S.1,Magnani Diogo M.1,Ricciardi Michael J.1,Bailey Varian K.1,Altman John D.9,Burton Dennis R.2456,Ejima Keisuke10,Allison David B.10,Evans David T.311,Rakasz Eva G.11,Parks Christopher L.7,Bonaldo Myrna C.8,Capuano Saverio11,Lifson Jeffrey D.12,Desrosiers Ronald C.1ORCID,Allen Todd M.2,Watkins David I.1

Affiliation:

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

2. Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA

3. Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA

4. Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA

5. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, USA

6. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, California, USA

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

8. Laboratório de Biologia Molecular de Flavivirus, Instituto Oswaldo Cruz—FIOCRUZ, Rio de Janeiro, Brazil

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

10. School of Public Health, Indiana University Bloomington, Bloomington, Indiana, USA

11. Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin, USA

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

Abstract

A better understanding of the immune correlates of protection against HIV might facilitate the development of a prophylactic vaccine. Therefore, we investigated simian immunodeficiency virus (SIV) infection outcomes in rhesus macaques expressing the major histocompatibility complex class I allele Mamu-B*17 . Approximately 21% of Mamu-B*17 + macaques spontaneously controlled chronic phase viremia after SIV infection, an effect that may involve CD8 + T cells targeting Mamu-B*17-restricted SIV epitopes. We vaccinated Mamu-B*17 + macaques with genes encoding immunodominant epitopes in Vif and Nef alone (group 1) or together with env (group 2). Although neither vaccine regimen prevented SIV infection, 5/8 group 2 vaccinees controlled viremia to below detection limits shortly after infection. This outcome, which was not observed in group 1, was associated with vaccine-induced, nonneutralizing Env-binding antibodies. Together, these findings suggest a limited contribution of Vif- and Nef-specific CD8 + T cells for virologic control in Mamu-B*17 + macaques and implicate anti-Env antibodies in containment 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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