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HIV vaccines induce CD8+ T cells with low antigen receptor sensitivity.
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.
Afiliação
  • Migueles SA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Nettere DM; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Gavil NV; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Wang LT; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Toulmin SA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Kelly EP; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Ward AJ; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Lin S; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Thompson SA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Peterson BA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Abdeen CS; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Sclafani CR; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Pryal PF; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Leach BG; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Ludwig AK; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Rogan DC; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Przygonska PA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Cattani A; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Imamichi H; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Sachs A; Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Cafri G; Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Huang NN; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Patamawenu A; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Liang CJ; Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Hallahan CW; Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Kambach DM; Agilent Technologies, Inc., Santa Clara, CA, USA.
  • Han EX; IsoPlexis, Inc., Branford, CT, USA.
  • Coupet T; IsoPlexis, Inc., Branford, CT, USA.
  • Chen J; IsoPlexis, Inc., Branford, CT, USA.
  • Moir SL; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Chun TW; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Coates EE; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Ledgerwood J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Schmidt J; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.
  • Taillandier-Coindard M; Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
  • Michaux J; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.
  • Pak H; Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
  • Bassani-Sternberg M; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.
  • Frahm N; Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
  • McElrath MJ; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.
  • Connors M; Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Science ; 382(6676): 1270-1276, 2023 12 15.
Article em En | MEDLINE | ID: mdl-38096385
ABSTRACT
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T Citotóxicos / Degranulação Celular / Infecções por HIV / Vacinas contra a AIDS / Citotoxicidade Imunológica Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T Citotóxicos / Degranulação Celular / Infecções por HIV / Vacinas contra a AIDS / Citotoxicidade Imunológica Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article