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
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Zusammenfassung: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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ISSN:1529-2908
1529-2916
1529-2916
DOI:10.1038/s41590-022-01163-9