Mamu-B*17+ rhesus macaques vaccinated with env, vif, and nef manifest early control of SIVmac239 replication

Mauricio Martins, Damien C. Tully, Núria Pedreño-Lopez, Benjamin von Bredow, Matthias G. Pauthner, Young C. Shin, Maoli Yuan, Noemia S. Lima, David J. Bean, Lucas Gonzalez-Nieto, Aline Domingues, Martin J. Gutman, Helen S. Maxwell, Diogo M. Magnani, Michael J. Ricciardi, Varian K. Bailey, John D. Altman, Dennis R. Burton, Keisuke Ejima, David B. AllisonDavid T. Evans, Eva G. Rakasz, Christopher L. Parks, Myrna C. Bonaldo, Saverio Capuano, Jeffrey D. Lifson, Ronald Charles Desrosiers, Todd M. Allen, David Watkins

Research output: Contribution to journalArticle

1 Scopus citations

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. In this study, 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, preexisting 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 on the unique mechanism of elite control in Mamu-B*17+ RMs and implicate vaccine-induced, nonneutralizing anti- Env antibodies in the containment of immunodeficiency virus infection.

Original languageEnglish (US)
Article numbere00690-18
JournalJournal of Virology
Volume92
Issue number16
DOIs
StatePublished - Aug 1 2018

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Keywords

  • AIDS
  • Human immunodeficiency virus
  • Simian immunodeficiency virus
  • Vaccines

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Martins, M., Tully, D. C., Pedreño-Lopez, N., Bredow, B. V., Pauthner, M. G., Shin, Y. C., Yuan, M., Lima, N. S., Bean, D. J., Gonzalez-Nieto, L., Domingues, A., Gutman, M. J., Maxwell, H. S., Magnani, D. M., Ricciardi, M. J., Bailey, V. K., Altman, J. D., Burton, D. R., Ejima, K., ... Watkins, D. (2018). Mamu-B*17+ rhesus macaques vaccinated with env, vif, and nef manifest early control of SIVmac239 replication. Journal of Virology, 92(16), [e00690-18]. https://doi.org/10.1128/JVI.00690-18