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|Title:||Mamu-B*17+ rhesus macaques vaccinated with env, vif, and nef manifest early control of SIVmac239 replication|
|Authors:||LIma, Noemia S.|
Bonaldo, Myrna C.
Múltipla autoria - ver em Notas
|Affilliation:||Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular de Flavivírus. Rio de Janeiro, RJ, Brasil.|
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular de Flavivírus. Rio de Janeiro, RJ, Brasil.
Múltipla autoria - ver em Notas
|Abstract:||Certain major histocompatibility complex class-I (MHC-I) alleles are associated with spontaneous control of viral replication in human immunodeficiency virus (HIV)-infected people and simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs). These cases of “elite” control of HIV/SIV replication are often immune-mediated, thereby providing a framework for studying anti-lentiviral immunity. Here we examined how vaccination impacts SIV replication in RMs expressing the MHC-I allele Mamu-B*17. Approximately 21% of Mamu-B*17+ and 50% of Mamu-B*08+ RMs control chronic phase viremia after SIVmac239 infection. Because CD8+ T-cells targeting Mamu-B*08-restricted SIV epitopes have been implicated in virologic suppression in Mamu-B*08+ RMs, we investigated whether this might also be true for Mamu-B*17+ RMs. Two groups of Mamu-B*17+ RMs were vaccinated with genes encoding Mamu-B*17-restricted epitopes in Vif and Nef. These genes were delivered by themselves (Group 1) or together with env (Group 2). Group 3 included MHC-I-matched RMs and served as the control group. Surprisingly, the Group 1 vaccine regimen had little effect on viral replication compared to Group 3, suggesting that, unlike Mamu-B*08+ RMs, pre-existing SIV-specific CD8+ T-cells alone do not facilitate long term virologic suppression in Mamu-B*17+ RMs. Remarkably, however, 5/8 Group 2 vaccinees controlled viremia to <15 viral RNA copies/mL soon after infection. No serological neutralizing activity against SIVmac239 was detected in Group 2, although vaccine-elicited gp140-binding antibodies correlated inversely with nadir viral loads. Collectively, these data shed new light into the unique mechanism of elite control in Mamu-B*17+ RMs and implicate vaccine-induced, non-neutralizing anti-Env antibodies in the containment of immunodeficiency virus infection.|
|Keywords:||Mamu-B*17+ rhesus macaques|
Non-neutralizing anti-Env antibodies
Simian immunodeficiency virus
|Publisher:||American Society for Microbiology|
|Citation:||MARTINS, Mauricio A. et al. Mamu-B*17+ rhesus macaques vaccinated 1 with env, vif, and nef manifest early control of SIVmac239 replication. J. Virol., p. 1-72, 6 June 2018.|
|Description:||AUTHORS - Mauricio A. Martins1*, Damien C. Tully2, Núria Pedreño-Lopez1, Benjamin von Bredow3, Matthias G. Pauthner4, Young C. Shin1, Maoli Yuan5, Noemia S. Lima6, David J. Bean2 , Lucas Gonzalez-Nieto1, Aline Domingues1, Martin J. Gutman1, Helen S. Maxwell1, Diogo M. Magnani1, Michael J. Ricciardi1, Varian K. Bailey1, John D. Altman7, Dennis R. Burton2,4, Keisuke Ejima8, David B. Allison8, David T. Evans3,9, Eva G. Rakasz9, Christopher L. Parks5, Myrna C. Bonaldo6, Saverio Capuano III9, Jeffrey D. Lifson10, Ronald C. Desrosiers1, Todd M. Allen2 , David I. Watkins1 - AFFILIATIONS - 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; IAVI Neutralizing Antibody Center; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID); The Scripps Research Institute, La Jolla, California, USA., 5 International AIDS Vaccine Initiative, AIDS Vaccine Design and Development Laboratory,Brooklyn, New York, USA, 6 Laboratório de Biologia Molecular de Flavivirus, Instituto Oswaldo Cruz–FIOCRUZ, Rio de Janeiro, Brazil 7 Department of Microbiology and Immunology, Emory University, Atlanta, Georgia, USA 8 School of Public Health, 24 Indiana University-Bloomington, Bloomington, Indiana, USA 9 Wisconsin National Primate Research Center, University of Wisconsin–Madison, Madison, Wisoncin, USA 10 AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.|
|Publication status:||Não publicado|
|Appears in Collections:||IOC - Preprint|
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