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

Mauricio Martins, Young C. Shin, Lucas Gonzalez-Nieto, Aline Domingues, Martin J. Gutman, Helen S. Maxwell, Iris Castro, Diogo M. Magnani, Michael Ricciardi, Nuria Pedreño-Lopez, Varian Bailey, Dillon Betancourt, John D. Altman, Matthias Pauthner, Dennis R. Burton, Benjamin von Bredow, David T. Evans, Maoli Yuan, Christopher L. Parks, Keisuke EjimaDavid B. Allison, Eva Rakasz, Glen N Barber, Saverio Capuano, Jeffrey D. Lifson, Ronald Charles Desrosiers, David Watkins

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Article numbere1006529
JournalPLoS Pathogens
Volume13
Issue number7
DOIs
StatePublished - Jul 1 2017

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Martins, M., Shin, Y. C., Gonzalez-Nieto, L., Domingues, A., Gutman, M. J., Maxwell, H. S., Castro, I., Magnani, D. M., Ricciardi, M., Pedreño-Lopez, N., Bailey, V., Betancourt, D., Altman, J. D., Pauthner, M., Burton, D. R., von Bredow, B., Evans, D. T., Yuan, M., Parks, C. L., ... Watkins, D. (2017). Vaccine-induced immune responses against both Gag and Env improve control of simian immunodeficiency virus replication in rectally challenged rhesus macaques. PLoS Pathogens, 13(7), [e1006529]. https://doi.org/10.1371/journal.ppat.1006529