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Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection.

Authors
  • Betts, Michael R
  • Exley, Barbara
  • Price, David A
  • Bansal, Anju
  • Camacho, Zenaido Tres
  • Teaberry, Vanessa
  • West, Sadie M
  • Ambrozak, David R
  • Tomaras, Georgia
  • Roederer, Mario
  • Kilby, J Michael
  • Tartaglia, Jim
  • Belshe, Robert
  • Gao, Feng
  • Douek, Daniel C
  • Weinhold, Kent J
  • Koup, Richard A
  • Goepfert, Paul
  • Ferrari, Guido
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Publication Date
Mar 22, 2005
Volume
102
Issue
12
Pages
4512–4517
Identifiers
PMID: 15753288
Source
Medline
License
Unknown

Abstract

Worldwide HIV-1 vaccine efforts are guided by the principle that HIV-specific T cell responses may provide protection from infection or delay overt disease. However, no clear correlates of T cell-mediated immune protection have been identified. Here, we examine in a HLA-B27(+) HIV seronegative vaccinee persistent HIV-specific vaccine-induced anti-Gag CD4(+) and CD8(+) T cell responses. Although these responses exhibited those characteristics (multifunctionality, appropriate memory phenotype, and targeting of epitopes associated with long-term nonprogression) predicted to correlate with protection from infection, the subject became HIV infected. After HIV infection, the vaccine-induced CD8(+) T cells expanded, but both CD4(+) and CD8(+) T cell responses acquired the functional and phenotypic patterns characteristic of chronic HIV infection. The virus quickly escaped the vaccine-induced T cell response, and the subject progressed more rapidly than expected for someone expressing the HLA-B27 allele. These data suggest that control of HIV by vaccine-elicited HIV-specific T cell responses may be difficult, even when the T cell response has those characteristics predicted to provide optimal protection.

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