HIV vaccines induce CD8+ T cells with low antigen receptor sensitivity

Science. 2023 Dec 15;382(6676):1270-1276. doi: 10.1126/science.adg0514. Epub 2023 Dec 14.

Abstract

Current HIV vaccines designed to stimulate CD8+ T cells have failed to induce immunologic control upon infection. The functions of vaccine-induced HIV-specific CD8+ T cells were investigated here in detail. Cytotoxic capacity was significantly lower than in HIV controllers and was not a consequence of low frequency or unaccumulated functional cytotoxic proteins. Low cytotoxic capacity was attributable to impaired degranulation in response to the low antigen levels present on HIV-infected targets. The vaccine-induced T cell receptor (TCR) repertoire was polyclonal and transduction of these TCRs conferred the same reduced functions. These results define a mechanism accounting for poor antiviral activity induced by these vaccines and suggest that an effective CD8+ T cell response may require a vaccination strategy that drives further TCR clonal selection.

MeSH terms

  • AIDS Vaccines* / immunology
  • Cell Degranulation* / immunology
  • Clone Cells
  • Cytotoxicity, Immunologic*
  • HIV Infections* / prevention & control
  • Humans
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes, Cytotoxic* / immunology

Substances

  • AIDS Vaccines
  • Receptors, Antigen, T-Cell