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Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine.
Li, Chunfeng; Lee, Audrey; Grigoryan, Lilit; Arunachalam, Prabhu S; Scott, Madeleine K D; Trisal, Meera; Wimmers, Florian; Sanyal, Mrinmoy; Weidenbacher, Payton A; Feng, Yupeng; Adamska, Julia Z; Valore, Erika; Wang, Yanli; Verma, Rohit; Reis, Noah; Dunham, Diane; O'Hara, Ruth; Park, Helen; Luo, Wei; Gitlin, Alexander D; Kim, Peter; Khatri, Purvesh; Nadeau, Kari C; Pulendran, Bali.
  • Li C; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Lee A; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Grigoryan L; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Arunachalam PS; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Scott MKD; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Trisal M; Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Wimmers F; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Sanyal M; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Weidenbacher PA; Department of Biochemistry & Stanford, ChEM-H, Stanford University, Stanford, CA, USA.
  • Feng Y; Department of Biochemistry & Stanford, ChEM-H, Stanford University, Stanford, CA, USA.
  • Adamska JZ; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Valore E; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Wang Y; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Verma R; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Reis N; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Dunham D; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • O'Hara R; Sean N. Parker Center for Allergy & Asthma Research, Stanford, CA, USA.
  • Park H; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
  • Luo W; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
  • Gitlin AD; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Kim P; Department of Physiological Chemistry, Genentech, South San Francisco, CA, USA.
  • Khatri P; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Nadeau KC; Department of Biochemistry & Stanford, ChEM-H, Stanford University, Stanford, CA, USA.
  • Pulendran B; Chan Zuckerberg Biohub, San Francisco, CA, USA.
Nat Immunol ; 23(4): 543-555, 2022 04.
Article in English | MEDLINE | ID: covidwho-1738613
ABSTRACT
Despite the success of the BNT162b2 mRNA vaccine, the immunological mechanisms that underlie its efficacy are poorly understood. Here we analyzed the innate and adaptive responses to BNT162b2 in mice, and show that immunization stimulated potent antibody and antigen-specific T cell responses, as well as strikingly enhanced innate responses after secondary immunization, which was concurrent with enhanced serum interferon (IFN)-γ levels 1 d following secondary immunization. Notably, we found that natural killer cells and CD8+ T cells in the draining lymph nodes are the major producers of this circulating IFN-γ. Analysis of knockout mice revealed that induction of antibody and T cell responses to BNT162b2 was not dependent on signaling via Toll-like receptors 2, 3, 4, 5 and 7 nor inflammasome activation, nor the necroptosis or pyroptosis cell death pathways. Rather, the CD8+ T cell response induced by BNT162b2 was dependent on type I interferon-dependent MDA5 signaling. These results provide insights into the molecular mechanisms by which the BNT162b2 vaccine stimulates immune responses.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines / CD8-Positive T-Lymphocytes Topics: Vaccines Limits: Animals / Humans Language: English Journal: Nat Immunol Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: S41590-022-01163-9

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines / CD8-Positive T-Lymphocytes Topics: Vaccines Limits: Animals / Humans Language: English Journal: Nat Immunol Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: S41590-022-01163-9