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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.


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.

SUBMITTER: Betts MR 

PROVIDER: S-EPMC552973 | biostudies-literature | 2005 Mar

REPOSITORIES: biostudies-literature

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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.

Betts Michael R MR   Exley Barbara B   Price David A DA   Bansal Anju A   Camacho Zenaido Tres ZT   Teaberry Vanessa V   West Sadie M SM   Ambrozak David R DR   Tomaras Georgia G   Roederer Mario M   Kilby J Michael JM   Tartaglia Jim J   Belshe Robert R   Gao Feng F   Douek Daniel C DC   Weinhold Kent J KJ   Koup Richard A RA   Goepfert Paul P   Ferrari Guido G  

Proceedings of the National Academy of Sciences of the United States of America 20050307 12


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  ...[more]

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