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

Current HIV vaccines designed to stimulate CD8+ T cells have failed to induce immunologic control upon infection. Functions of vaccine-induced HIV-specific CD8+ T cells were investigated here in detail. HIV-specific CD8+ T-cell cytotoxic capacity was extremely low and was not a consequence of low frequency nor lack of accumulation of functional perforin (PRF) or granzyme B (GrB). Low cytotoxic capacity was attributable to impaired degranulation in response to the low levels of antigen present on HIV-infected CD4+ T cells. The T cell receptor (TCR) repertoire induced by these vaccines was polyclonal and transduction of these TCRs conferred the same reduced functions. These results define a mechanism accounting for the poor antiviral activity induced by these vaccines and suggest that an effective CD8+ T-cell response may require more intensive antigenic stimulation.