Rare Control of SIVmac239 Infection in a Vaccinated Rhesus Macaque

Mauricio A. Martins, Damien C. Tully, Young C. Shin, Lucas Gonzalez-Nieto, Kim L. Weisgrau, David J. Bean, Rujuta Gadgil, Martin J. Gutman, Aline Domingues, Helen S. Maxwell, Diogo M. Magnani, Michael Ricciardi, Nuria Pedreño-Lopez, Varian Bailey, Michael A. Cruz, Noemia S. Lima, Myrna C. Bonaldo, John D. Altman, Eva Rakasz, Saverio CapuanoKeith A. Reimann, Michael Piatak, Jeffrey D. Lifson, Ronald C. Desrosiers, Todd M. Allen, David I. Watkins

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Effector memory T cell (TEM) responses display potent antiviral propertis and have been linked to stringent control of simian immunodeficiency virus (SIV) replication. Since recurrent antigen stimulation drives the differentiation of CD8+ T cells toward the TEM phenotype, in this study we incorporated a persistent herpesviral vector into a heterologous prime/boost/boost vaccine approach to maximize the induction of TEM responses. This new regimen resulted in CD8+ TEM-biased responses in four rhesus macaques, three of which controlled viral replication to <1,000 viral RNA copies/ml of plasma for more than 6 months after infection with SIVmac239. Over the course of this study, we made a series of interesting observations in one of these successful controller animals. Indeed, in vivo elimination of CD8αβ+ T cells using a new CD8β-depleting antibody did not abrogate virologic control in this monkey. Only after its CD8α+ lymphocytes were depleted did SIV rebound, suggesting that CD8αα+ but not CD8αβ+ cells were controlling viral replication. By 2 weeks postinfection (PI), the only SIV sequences that could be detected in this animal harbored a small in-frame deletion in nef affecting six amino acids. Deep sequencing of the SIVmac239 challenge stock revealed no evidence of this polymorphism. However, sequencing of the rebound virus following CD8α depletion at week 38.4 PI again revealed only the six-amino acid deletion in nef. While any role for immunological pressure on the selection of this deleted variant remains uncertain, our data provide anecdotal evidence that control of SIV replication can be maintained without an intact CD8αβ+ T cell compartment.

Original languageEnglish (US)
Pages (from-to)843-858
Number of pages16
JournalAIDS research and human retroviruses
Volume33
Issue number8
DOIs
StatePublished - Aug 2017

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Keywords

  • HIV/AIDS
  • SIV vaccine
  • lymphocyte depletion
  • nonhuman primate

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

Cite this

Martins, M. A., Tully, D. C., Shin, Y. C., Gonzalez-Nieto, L., Weisgrau, K. L., Bean, D. J., Gadgil, R., Gutman, M. J., Domingues, A., Maxwell, H. S., Magnani, D. M., Ricciardi, M., Pedreño-Lopez, N., Bailey, V., Cruz, M. A., Lima, N. S., Bonaldo, M. C., Altman, J. D., Rakasz, E., ... Watkins, D. I. (2017). Rare Control of SIVmac239 Infection in a Vaccinated Rhesus Macaque. AIDS research and human retroviruses, 33(8), 843-858. https://doi.org/10.1089/aid.2017.0046