HIV vaccines induce CD8 + T cells with low antigen receptor sensitivity.
Stephen A MiguelesDanielle M NettereNoah V GavilLawrence T WangSushila A ToulminElizabeth P KellyAddison J WardSiying LinSarah A ThompsonBennett A PetersonCassidy S AbdeenCarina R SclafaniPatrick F PryalBenjamin G LeachAmanda K LudwigDaniel C RoganPaulina A PrzygonskaAngela CattaniHiromi ImamichiAbraham SachsGal CafriNing-Na HuangAndy PatamawenuC Jason LiangClaire W HallahanDiane M KambachEdward X HanTiffany CoupetJonathan ChenSusan L MoirTae-Wook ChunEmily E CoatesJulie LedgerwoodJulien SchmidtMarie Taillandier-CoindardJustine MichauxHuiSong PakMichal Bassani-SternbergNicole FrahmM Juliana McElrathMark ConnorsPublished in: Science (New York, N.Y.) (2023)
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.