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

PLoS Pathogens

Ronald C. Desrosiers¹  Saverio Capuano III²  Matthias Pauthner³  Dennis R. Burton³  John D. Altman⁴  Dillon Betancourt⁵  David T. Evans⁶  Benjamin von Bredow⁶  Mauricio A. Martins⁷  Nuria Pedreño-Lopez⁷  David I. Watkins⁷  Michael Ricciardi⁷  Martin J. Gutman⁷  Iris Castro⁷  Young C. Shin⁷  Helen S. Maxwell⁷  Varian Bailey⁷  Lucas Gonzalez-Nieto⁷  Diogo M. Magnani⁷  Aline Domingues⁷  Christopher L. Parks⁸  Keisuke Ejima⁸  Eva Rakasz⁹  David B. Allison⁹  Glen N. Barber^1,10  Jeffrey D. Lifson^1,10  Maoli Yuan^1,10 

[1] AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America;Department of Cell Biology, University of Miami, Miami, Florida, United States of America;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;Department of Microbiology and Immunology, Emory University, Atlanta, Georgia, United States of America;Department of Microbiology and Immunology, University of Miami, Miami, Florida, United States of America;Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison, Madison, Wisconsin, United States of America;Department of Pathology, University of Miami, Miami, Florida, United States of America;International AIDS Vaccine Initiative, AIDS Vaccine Design and Development Laboratory, Brooklyn, New York, United States of America;Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America;Wisconsin National Primate Research Center, University of Wisconsin–Madison, Madison, Wisconsin, United States of America

关键词: Macaque;    T cells;    SIV;    Cytotoxic T cells;    Monkeys;    Antibodies;    Immune response;    Viral replication;   

DOI  :  10.1371/journal.ppat.1006529

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY