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

Dataset DOI: [10.5061/dryad.v41ns1s2b](https://doi.org/10.5061/dryad.v41ns1s2b)

## Description of the data and file structure

HIV-specific CD8+ T cell responses in HIV vaccine recipients are compared with those of chronically infected long-term nonprogressors / elite controllers (LTNP/EC) and progressors specifically as they relate to the response to HIV-infected autologous primary CD4+ T cell targets. LTNP/ECs represent a rare population of people living with HIV who maintain durable control over HIV replication without antiretroviral therapy. A variety of experimental assays employing subject derived peripheral blood mononuclear cells (PBMCs) were used in these investigations. Relative to chronically infected patients, we found that the CD8+ T cells induced by HIV vaccines exhibited lower cytotoxic capacity due to impaired degranulation and perforin polarization to the immunologic synapse. This was associated ...