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.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- March 2005
- DOI:
- 10.1073/pnas.0408773102
- Bibcode:
- 2005PNAS..102.4512B
- Keywords:
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- IMMUNOLOGY