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During chronic HIV-1 infection, continuing viral replication is associated with impaired proliferative capacity of virus-specific CD8+ T cells and with the expansion and persistence of oligoclonal T cell populations. TCR usage may significantly influence CD8+ T cell-mediated control of AIDS viruses; however, the potential to modulate the repertoire of functional virus-specific T cells by immunotherapy has not been explored. To investigate this, we analyzed the TCR Vbeta usage of CD8+ T cells populations which were expanded following vaccination with modified vaccinia virus Ankara expressing a HIV-1 gag/multiepitope immunogen (MVA.HIVA) in HIV-1-infected patients receiving highly active antiretroviral therapy. Vaccinations induced the re-expansion of HIV-1-specific CD8+ T cells and these showed broad TCR Vbeta usage which was maintained for at least 1 year in some individuals. By contrast, virus-specific CD8+ T cell populations in the same donors which failed to expand after vaccination and in unvaccinated controls were oligoclonal. Simultaneously, we observed that CD8+ T cells recognizing vaccine-derived HIV-1 epitopes displayed enhanced capacity to proliferate and to inhibit HIV-1 replication in vitro, following MVA.HIVA immunizations. Taken together, these data indicate that an attenuated viral-vectored vaccine can modulate adaptive CD8+ T cell responses to HIV-1 and improve their antiviral functional capacity. The potential therapeutic benefit of this vaccination approach warrants further investigation.

Original publication

DOI

10.4049/jimmunol.179.1.597

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

07/2007

Volume

179

Pages

597 - 606

Addresses

Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.

Keywords

CD8-Positive T-Lymphocytes, Humans, HIV-1, HIV Infections, Chronic Disease, Gene Products, nef, Receptors, Antigen, T-Cell, alpha-beta, Gene Products, gag, Gene Products, pol, AIDS Vaccines, Epitopes, T-Lymphocyte, Antiretroviral Therapy, Highly Active, Cell Proliferation, Genes, T-Cell Receptor beta, nef Gene Products, Human Immunodeficiency Virus