Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine

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 wel...

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Veröffentlicht in:	Nature immunology Jg. 23; H. 4; S. 543 - 555
Hauptverfasser:	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
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Nature Publishing Group 01.04.2022
Schlagworte:	Adaptive Immunity Animals Antigens BNT162 Vaccine CD8 antigen CD8-Positive T-Lymphocytes Cell death Coronaviruses COVID-19 Humans Immunity, Innate Immunization Inflammasomes Innate immunity Lymph nodes Lymphocytes Lymphocytes T Mice Molecular modelling mRNA mRNA Vaccines Natural killer cells Necroptosis Pyroptosis Toll-like receptors Vaccines Vaccines, Synthetic γ-Interferon
ISSN:	1529-2908, 1529-2916, 1529-2916
Online-Zugang:	Volltext
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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.
AbstractList	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.How mRNA-based coronavirus disease 2019 vaccines drive immune responses is not clear. Here the authors characterize immune responses to the BNT162b2 vaccine in mice, and show how it stimulates innate immunity, with antigen-specific CD8+ T cell responses dependent on the RNA sensor MDA5. 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. 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.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.
Author	Wang, Yanli Weidenbacher, Payton A Grigoryan, Lilit Arunachalam, Prabhu S Wimmers, Florian Dunham, Diane O'Hara, Ruth Khatri, Purvesh Pulendran, Bali Adamska, Julia Z Park, Helen Gitlin, Alexander D Lee, Audrey Feng, Yupeng Reis, Noah Scott, Madeleine K D Kim, Peter Li, Chunfeng Sanyal, Mrinmoy Luo, Wei Nadeau, Kari C Valore, Erika Verma, Rohit Trisal, Meera
Author_xml	– sequence: 1 givenname: Chunfeng surname: Li fullname: Li, Chunfeng organization: Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA – sequence: 2 givenname: Audrey surname: Lee fullname: Lee, Audrey organization: Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA – sequence: 3 givenname: Lilit surname: Grigoryan fullname: Grigoryan, Lilit organization: Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA – sequence: 4 givenname: Prabhu S orcidid: 0000-0003-0090-5689 surname: Arunachalam fullname: Arunachalam, Prabhu S organization: Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA – sequence: 5 givenname: Madeleine K D surname: Scott fullname: Scott, Madeleine K D organization: Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA – sequence: 6 givenname: Meera surname: Trisal fullname: Trisal, Meera organization: Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA – sequence: 7 givenname: Florian orcidid: 0000-0002-6482-2228 surname: Wimmers fullname: Wimmers, Florian organization: Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA – sequence: 8 givenname: Mrinmoy orcidid: 0000-0002-1365-4279 surname: Sanyal fullname: Sanyal, Mrinmoy organization: Department of Biochemistry & Stanford, ChEM-H, Stanford University, Stanford, CA, USA – sequence: 9 givenname: Payton A surname: Weidenbacher fullname: Weidenbacher, Payton A organization: Department of Biochemistry & Stanford, ChEM-H, Stanford University, Stanford, CA, USA – sequence: 10 givenname: Yupeng orcidid: 0000-0001-8550-2787 surname: Feng fullname: Feng, Yupeng organization: Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA – sequence: 11 givenname: Julia Z surname: Adamska fullname: Adamska, Julia Z organization: Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA – sequence: 12 givenname: Erika surname: Valore fullname: Valore, Erika organization: Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA – sequence: 13 givenname: Yanli surname: Wang fullname: Wang, Yanli organization: Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA – sequence: 14 givenname: Rohit surname: Verma fullname: Verma, Rohit organization: Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA – sequence: 15 givenname: Noah orcidid: 0000-0002-7258-2463 surname: Reis fullname: Reis, Noah organization: Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA – sequence: 16 givenname: Diane surname: Dunham fullname: Dunham, Diane organization: Sean N. Parker Center for Allergy & Asthma Research, Stanford, CA, USA – sequence: 17 givenname: Ruth surname: O'Hara fullname: O'Hara, Ruth organization: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA – sequence: 18 givenname: Helen surname: Park fullname: Park, Helen organization: Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA – sequence: 19 givenname: Wei surname: Luo fullname: Luo, Wei organization: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA – sequence: 20 givenname: Alexander D orcidid: 0000-0002-9229-0919 surname: Gitlin fullname: Gitlin, Alexander D organization: Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA – sequence: 21 givenname: Peter surname: Kim fullname: Kim, Peter organization: Chan Zuckerberg Biohub, San Francisco, CA, USA – sequence: 22 givenname: Purvesh orcidid: 0000-0002-4143-4708 surname: Khatri fullname: Khatri, Purvesh organization: Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA – sequence: 23 givenname: Kari C orcidid: 0000-0002-2146-2955 surname: Nadeau fullname: Nadeau, Kari C organization: Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford, CA, USA – sequence: 24 givenname: Bali orcidid: 0000-0001-6517-4333 surname: Pulendran fullname: Pulendran, Bali email: bpulend@stanford.edu, bpulend@stanford.edu, bpulend@stanford.edu organization: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA. bpulend@stanford.edu
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/35288714$$D View this record in MEDLINE/PubMed
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Snippet	Despite the success of the BNT162b2 mRNA vaccine, the immunological mechanisms that underlie its efficacy are poorly understood. Here we analyzed the innate...
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SubjectTerms	Adaptive Immunity Animals Antigens BNT162 Vaccine CD8 antigen CD8-Positive T-Lymphocytes Cell death Coronaviruses COVID-19 Humans Immunity, Innate Immunization Inflammasomes Innate immunity Lymph nodes Lymphocytes Lymphocytes T Mice Molecular modelling mRNA mRNA Vaccines Natural killer cells Necroptosis Pyroptosis Toll-like receptors Vaccines Vaccines, Synthetic γ-Interferon
Title	Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine
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