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Author Notes:

E-mail: mmartins@med.miami.edu

See publication for full list of author contributions.

We thank Teresa Maidana Giret for confirming the MHC-I genotype of the monkeys in this study; Leydi Guzman for administrative assistance; Jessica Furlott, Kelli Oswald, Rebecca Shoemaker, Randy Fast, Mary Lopez, Raiza Bastidas, and Marina Kemelman for excellent technical support.

Peng Li for assistance with statistical analyses; Eric Peterson, Kristin Crosno, Wendy Newton, and Dane Schalk for taking excellent care of the rhesus macaques used in the present experiment.

DL is employed by Leidos Biomedical Research, Inc., the Prime Contractor for the Operations and Technical Support Contract for the Frederick National Laboratory for Cancer Research, which exists solely to operate the FNLCR on behalf of the National Cancer Institute and National Institutes of Health.

There are no competing interests or relevant declarations related to employment, consultancy, patents, products in development or marketed products.

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Research Funding:

This work was funded by Public Health Service grant P01 AI094420 from the National Institute of Allergy and Infectious Diseases and was supported in part by federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E.

This work was also partially funded by the International AIDS Vaccine Initiative (IAVI) with the generous support from many donors including: The Bill & Melinda Gates Foundation; the Ministry of Foreign Affairs of Denmark; Irish Aid; the Ministry of Finance of Japan; the Ministry of Foreign Affairs of the Netherlands; the Norwegian Agency for Development Cooperation (NORAD); the United Kingdom Department for International Development (DFID), and the United States Agency for International Development (USAID).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Microbiology
  • Parasitology
  • Virology
  • T-CELL RESPONSES
  • VESICULAR STOMATITIS-VIRUS
  • HIGHLY PATHOGENIC SIV
  • VIRAL LOAD
  • DISCORDANT ASSOCIATIONS
  • INTRARECTAL CHALLENGE
  • SIVMAC251 ACQUISITION
  • CORRELATES ANALYSIS
  • INFECTED-CELLS
  • EFFICACY TRIAL

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

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Journal Title:

PLoS Pathogens

Volume:

Volume 13, Number 7

Publisher:

, Pages e1006529-e1006529

Type of Work:

Article | Final Publisher PDF

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.

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© 2017 Public Library of Science. All Rights Reserved.

This is an Open Access work distributed under the terms of the Creative Commons Universal : Public Domain Dedication License (http://creativecommons.org/publicdomain/zero/1.0/).

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