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PLoS Pathog. 2017 Jul 21;13(7):e1006529. doi: 10.1371/journal.ppat.1006529. eCollection 2017 Jul.

Vaccine-induced immune responses against both Gag and Env improve control of simian immunodeficiency virus replication in rectally challenged rhesus macaques.

Author information

1
Department of Pathology, University of Miami, Miami, Florida, United States of America.
2
Department of Microbiology and Immunology, University of Miami, Miami, Florida, United States of America.
3
Department of Microbiology and Immunology, Emory University, Atlanta, Georgia, United States of America.
4
Department of Immunology and Microbiology, IAVI Neutralizing Antibody Center, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, California, United States of America.
5
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
6
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
7
International AIDS Vaccine Initiative, AIDS Vaccine Design and Development Laboratory, Brooklyn, New York, United States of America.
8
Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
9
Department of Cell Biology, University of Miami, Miami, Florida, United States of America.
10
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.

Abstract

The ability to control lentivirus replication may be determined, in part, by the extent to which individual viral proteins are targeted by the immune system. Consequently, defining the antigens that elicit the most protective immune responses may facilitate the design of effective HIV-1 vaccines. Here we vaccinated four groups of rhesus macaques with a heterologous vector prime/boost/boost/boost (PBBB) regimen expressing the following simian immunodeficiency virus (SIV) genes: env, gag, vif, rev, tat, and nef (Group 1); env, vif, rev, tat, and nef (Group 2); gag, vif, rev, tat, and nef (Group 3); or vif, rev, tat, and nef (Group 4). Following repeated intrarectal challenges with a marginal dose of the neutralization-resistant SIVmac239 clone, vaccinees in Groups 1-3 became infected at similar rates compared to control animals. Unexpectedly, vaccinees in Group 4 became infected at a slower pace than the other animals, although this difference was not statistically significant. Group 1 exhibited the best post-acquisition virologic control of SIV infection, with significant reductions in both peak and chronic phase viremia. Indeed, 5/8 Group 1 vaccinees had viral loads of less than 2,000 vRNA copies/mL of plasma in the chronic phase. Vaccine regimens that did not contain gag (Group 2), env (Group 3), or both of these inserts (Group 4) were largely ineffective at decreasing viremia. Thus, vaccine-induced immune responses against both Gag and Env appeared to maximize control of immunodeficiency virus replication. Collectively, these findings are relevant for HIV-1 vaccine design as they provide additional insights into which of the lentiviral proteins might serve as the best vaccine immunogens.

PMID:
28732035
PMCID:
PMC5540612
DOI:
10.1371/journal.ppat.1006529
[Indexed for MEDLINE]
Free PMC Article

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