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

• 成果类型: Article
• 署名作者: Migueles, Stephen A.; Nettere, Danielle M.; Gavil, Noah V.; Wang, Lawrence T.; Toulmin, Sushila A.; Kelly, Elizabeth P.; Ward, Addison J.; Lin, Siying; Thompson, Sarah A.; Peterson, Bennett A.; Abdeen, Cassidy S.; Sclafani, Carina R.; Pryal, Patrick F.; Leach, Benjamin G.; Ludwig, Amanda K.; Rogan, Daniel C.; Przygonska, Paulina A.; Cattani, Angela; Imamichi, Hiromi; Sachs, Abraham; Cafri, Gal; Huang, Ning-Na; Patamawenu, Andy; Liang, C. Jason; Hallahan, Claire W.; Kambach, Diane M.; Han, Edward X.; Coupet, Tiffany; Chen, Jonathan; Moir, Susan L.; Chun, Tae-Wook; Coates, Emily E.; Ledgerwood, Julie; Schmidt, Julien; Taillandier-Coindard, Marie; Michaux, Justine; Pak, HuiSong; Bassani-Sternberg, Michal; Frahm, Nicole; McElrath, M. Juliana; Connors, Mark
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Agilent Technologies; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Ludwig Institute for Cancer Research; University of Lausanne; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Fred Hutchinson Cancer Center; Duke University; University of Minnesota System; University of Minnesota Twin Cities; University of Massachusetts System; University of Massachusetts Worcester
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8578
• DOI: 10.1126/science.adg0514
• 发表日期: 2023-12-15
• 页码: 1270-1276
• 关键词: functional-avidity; mediated-immunity; clonotypes; lymphocytes; vaccination; expression; frequency; responses; efficacy; therapy

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.