作者
Stephen A. Migueles,Danielle Nettere,Noah Veis Gavil,Lawrence T. Wang,Sushila A. Toulmin,Eileen A. Kelly,Addison J. Ward,Siying Lin,Sarah Thompson,Bennett A. Peterson,Cassidy S. Abdeen,Carina R. Sclafani,Patrick F. Pryal,Brandie Heald,Amanda K. Ludwig,Daniel C Rogan,Paulina A. Przygonska,Angela Cattani,Hiromi Imamichi,Abraham Sachs,Gal Cafri,Ning‐Na Huang,Andy Patamawenu,Chi‐Hui Liang,Claire W. Hallahan,Diane M. Kambach,Edward X. Han,Tiffany A. Coupet,Jonathan Chen,Susan Moir,Tae‐Wook Chun,Emily E. Coates,Julie E. Ledgerwood,Julien Schmidt,Marie Taillandier-Coindard,Justine Michaux,HuiSong Pak,Michal Bassani-Sternberg,Nicole Frahm,M. Juliana McElrath,Mark Connors
摘要
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.