Recombinant vector-induced HIV/SIV-specific CD4+ T lymphocyte responses in rhesus monkeys

Yue Sun, Sampa Santra, Adam P. Buzby, John R. Mascola, Gary J. Nabel, Norman L. Letvin

Research output: Contribution to journalArticle

Abstract

The recently reported modest success of the RV144 Thai trial vaccine regimen in preventing HIV-1 acquisition has focused interest on the potential contribution to that protection of vaccine-elicited CD4+ T cell responses. We evaluated the induction of virus-specific CD4+ T cell responses in rhesus monkeys using a series of diverse vaccine vectors. We assessed both the magnitudes and functional profiles of the antigen-specific CD4+ T cells by measuring cytokine production, memory differentiation, and the expression of mucosal homing molecules. We found that DNA prime/recombinant MVA boost immunizations induced particularly high-frequency virus-specific CD4+ T cell responses with polyfunctional repertoires, and these responses were partially preserved following SHIV-89.6P challenge. The majority of the vaccine-elicited CD4+ T cells were CD28+ memory T cells that expressed low levels of β7. Neither the magnitudes nor the functional profiles of the virus-specific CD4+ T cells generated by vaccination were associated with a preservation of CD4+ T cells or control of viral replication following SHIV-89.6P challenge. Interestingly, monkeys primed with recombinant Ad5 immunogens showed a dramatic expansion of both the magnitude and polyfunctionality of the vaccine-elicited CD4+ T cell responses following envelope protein boost. These results demonstrate that vaccine strategies that include recombinant MVA or recombinant Ad5 vectors can elicit robust CD4+ T cell responses.

Original languageEnglish (US)
Pages (from-to)48-55
Number of pages8
JournalVirology
Volume406
Issue number1
DOIs
StatePublished - Oct 2010
Externally publishedYes

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Keywords

  • CD4 T cell responses
  • HIV vaccine
  • Rhesus monkey
  • SHIV-89.6P

ASJC Scopus subject areas

  • Virology
  • Medicine(all)

Cite this

Sun, Y., Santra, S., Buzby, A. P., Mascola, J. R., Nabel, G. J., & Letvin, N. L. (2010). Recombinant vector-induced HIV/SIV-specific CD4+ T lymphocyte responses in rhesus monkeys. Virology, 406(1), 48-55. https://doi.org/10.1016/j.virol.2010.07.004