Absence of immunodominant anti-gag p17 (SL9) responses among gag CTL-positive, HIV-uninfected vaccine recipients expressing the HLA-A*0201 allele

Academic Article

Abstract

  • According to a number of previous reports, control of HIV replication in humans appears to be linked to the presence of anti-HIV-1 Gag-specific CD8 responses. During the chronic phase of HIV-1 infection, up to 75% of the HIV-infected individuals who express the histocompatibility leukocyte Ag (HLA)-A*0201 recognize the Gag p17 SLYNTVATL (aa residues 77-85) epitope (SL9). However, the role of the anti-SL9 CD8 CTL in controlling HIV-1 infection remains controversial. In this study we determined whether the pattern of SL9 immunodominance in uninfected, HLA-A*0201 HIV vaccine recipients is similar to that seen in chronically HIV-infected subjects. The presence of anti-SL9 responses was determined using a panel of highly sensitive cellular immonoassays, including peptide:MHC tetramer binding, IFN-γ ELISPOT, and cytokine flow cytometry. Thirteen HLA-A*0201 vaccinees with documented anti-Gag CD8 CTL reactivities were tested, and none had a delectable anti-SL9 response. These findings strongly suggest that the pattern of SL9 epitope immunodominance previously reported among chronically infected, HLA-A*0201-positive patients is not recapitulated in noninfected recipients of Gag-containing canarypox-based candidate vaccines and may be influenced by the relative immimogenicity of these constructs.
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    Digital Object Identifier (doi)

    Author List

  • Ferrari G; Neal W; Ottinger J; Jones AM; Edwards BH; Goepfert P; Betts MR; Koup RA; Buchbinder S; McElrath MJ
  • Start Page

  • 2126
  • End Page

  • 2133
  • Volume

  • 173
  • Issue

  • 3