An algorithm for evaluating human cytotoxic T lymphocyte responses to candidate AIDS vaccines

Lucy M. Carruth, Tim F. Greten, Cristin E. Murray, Monica G. Castro, Sylvia N. Crone, Wendy Pavlat, Jonathan P. Schneck, Robert F. Siliciano

Research output: Contribution to journalArticlepeer-review

Abstract

Development of an effective vaccine against HIV-1 will likely require the induction of a broad array of immune responses, including virus-specific CTLs and neutralizing antibodies. One promising vaccine approach involves live recombinant canarypox (CP)-based vectors (ALVAC) containing multiple HIV-1 genes. In phase I clinical trials in HIV-1-seronegative volunteers, the cumulative rate of detection of HIV-1-specific CTLs has been as high as 60- 70%. In the present study, the factors associated with CTL responsiveness were evaluated in a subset of vaccinees immunized with a CP vector expressing portions of the gag, pro, and env genes of HIV-1 (ALVAC-HIV). CTL responses were detected in one of seven examined. While the responding individual had both CD4+ and CD8+ CTLs directed at multiple HIV-1 antigens, this response was not detectable 1 year after the last vaccination. In-depth characterization of 'CTL nonresponders' showed that nonresponsiveness was not associated with defects in antigen processing or presentation. A generalized defect in CTL responsiveness was ruled out by parallel assays to detect CMV- specific CTLs from these same volunteers. Furthermore, HIV-1-specific memory CTLs were not detectable by peptide stimulation or by a novel technique for flow cytometric visualization of Gag epitope-specific T lymphocytes while HIV-1-seropositive donors frequently had 0.1-3% of CD8+ cells stain positively for this epitope (SLYNTVATL). Taken together, these results suggest that the lack of detectable HIV-1 CTLs in these volunteers was not due to classic MHC-linked nonresponsiveness.

Original languageEnglish (US)
Pages (from-to)1021-1034
Number of pages14
JournalAIDS research and human retroviruses
Volume15
Issue number11
DOIs
StatePublished - Jul 20 1999

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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