1. Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection.
- Author
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Betts MR, Exley B, Price DA, Bansal A, Camacho ZT, Teaberry V, West SM, Ambrozak DR, Tomaras G, Roederer M, Kilby JM, Tartaglia J, Belshe R, Gao F, Douek DC, Weinhold KJ, Koup RA, Goepfert P, and Ferrari G
- Subjects
- AIDS Vaccines genetics, AIDS Vaccines immunology, Adult, Amino Acid Sequence, Base Sequence, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, DNA, Viral genetics, Gene Products, gag genetics, HIV Infections genetics, HIV Infections transmission, HIV Seronegativity immunology, HIV-1 genetics, HLA-B27 Antigen metabolism, Humans, Male, Molecular Sequence Data, Phenotype, AIDS Vaccines pharmacology, HIV Infections immunology, HIV Infections prevention & control, HIV-1 immunology, T-Lymphocytes immunology
- 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.
- Published
- 2005
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