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

• Type of Material: Article
• Authors: Mauricio A. Martins, University of Miami; Young C. Shin, University of Miami; Lucas Gonzalez-Nieto, University of Miami; Aline Domingues, University of Miami; Martin J. Gutman, University of Miami; Helen S. Maxwell, University of Miami; Iris Castro, University of Miami; Diogo M. Magnani, University of Miami; Michael Ricciardi, University of Miami; Nuria Pedreño-Lopez, University of Miami; Varian Bailey, University of Miami; Dillon Betancourt, University of Miami; John Altman, Emory University; Matthias Pauthner, Scripps Research Institute; Dennis R. Burton, Scripps Research Institute; Benjamin von Bredow, University of Wisconsin-Madison; David T. Evans, University of Wisconsin-Madison; Maoli Yuan, International AIDS Vaccine Initiative, AIDS Vaccine Design and Development Laboratory; Christopher L. Parks, International AIDS Vaccine Initiative, AIDS Vaccine Design and Development Laboratory; Keisuke Ejima, University of Alabama Birmingham; David B. Allison, University of Alabama Birmingham; Eva Rakasz, University of Wisconsin-Madison; Glen N. Barber, University of Miami; Saverio Capuano, University of Wisconsin-Madison; Jeffrey D. Lifson, Frederick National Laboratory for Cancer Research; Ronald C. Desrosiers, University of Miami; David I. Watkins, University of Miami
• Language: English
• Date: 2017-07-01
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2017 Public Library of Science. All Rights Reserved.
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.ppat.1006529
• Title of Journal or Parent Work: PLoS Pathogens
• ISSN: 1553-7366
• Volume: 13
• Issue: 7
• Start Page: e1006529
• End Page: e1006529
• Grant/Funding Information: 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: Parasitology; Microbiology; T-CELL RESPONSES; SIVMAC251 ACQUISITION; Science & Technology; INFECTED-CELLS; Life Sciences & Biomedicine; Virology; INTRARECTAL CHALLENGE; HIGHLY PATHOGENIC SIV; DISCORDANT ASSOCIATIONS; VIRAL LOAD; EFFICACY TRIAL; VESICULAR STOMATITIS-VIRUS; CORRELATES ANALYSIS
• Research Categories: Health Sciences, Immunology; Biology, Microbiology; Health Sciences, Pathology

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.