Immunization with live attenuated simian immunodeficiency virus induces strong type 1 T helper responses and β-chemokine production

Marie Claire Gauduin, Rhona L. Glickman, Shabbir Ahmad, Tilahun Yilma, R. Paul Johnson

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Immunization with live attenuated simian immunodeficiency virus (SIV) strains has proved to be one of the most effective strategies to induce protective immunity in the SIV/macaque model. To better understand the role that CD4+ T helper responses may play in mediating protection in this model, we characterized SIV-specific proliferative and cytokine responses in macaques immunized with live attenuated SIV strains. Macaques chronically infected with live attenuated SIV had strong proliferative responses to SIV proteins, with stimulation indices of up to 74. The magnitude of the proliferative response to SIV Gag varied inversely with the degree of attenuation; Gag-specific but not envelope-specific responses were lower in animals infected with more highly attenuated SIV strains. SIV-specific stimulation of lymphocytes from vaccinated macaques resulted in secretion of interferon-γ, IL-2, regulated-upon-activation, normal T cells expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1α, and MIP-1β but not IL-4 or IL-10. Intracellular flow cytometric analysis documented that, in macaques vaccinated with SIVmac2392Δnef, up to 2% of all CD4+T cells were specific for SIV p55. The ability of live attenuated SIV to induce a strong, sustained type 1 T helper response may play a role in the success of this vaccination approach to generate protection against challenge with wild-type SIV.

Original languageEnglish (US)
Pages (from-to)14031-14036
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number24
DOIs
StatePublished - Nov 23 1999

ASJC Scopus subject areas

  • Genetics
  • General

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