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

dc.contributor.authorLi, Chunfeng
dc.contributor.authorLee, Audrey
dc.contributor.authorGrigoryan, Lilit
dc.contributor.authorArunachalam, Prabhu S.
dc.contributor.authorScott, Madeleine K.D.
dc.contributor.authorTrisal, Meera
dc.contributor.authorWimmers, Florian
dc.contributor.authorSanyal, Mrinmoy
dc.contributor.authorWeidenbacher, Payton A.
dc.contributor.authorFeng, Yupeng
dc.contributor.authorAdamska, Julia Z.
dc.contributor.authorValore, Erika
dc.contributor.authorWang, Yanli
dc.contributor.authorVerma, Rohit
dc.contributor.authorReis, Noah
dc.contributor.authorDunham, Diane
dc.contributor.authorO’Hara, Ruth
dc.contributor.authorPark, Helen
dc.contributor.authorLuo, Wei
dc.contributor.authorGitlin, Alexander D.
dc.contributor.authorKim, Peter
dc.contributor.authorKhatri, Purvesh
dc.contributor.authorNadeau, Kari C.
dc.contributor.authorPulendran, Bali
dc.contributor.departmentMicrobiology and Immunology, School of Medicine
dc.date.accessioned2023-09-04T10:38:45Z
dc.date.available2023-09-04T10:38:45Z
dc.date.issued2022
dc.description.abstractDespite 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.
dc.eprint.versionAuthor's manuscript
dc.identifier.citationLi C, Lee A, Grigoryan L, et al. Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine. Nat Immunol. 2022;23(4):543-555. doi:10.1038/s41590-022-01163-9
dc.identifier.urihttps://hdl.handle.net/1805/35351
dc.language.isoen_US
dc.publisherSpringer Nature
dc.relation.isversionof10.1038/s41590-022-01163-9
dc.relation.journalNature Immunology
dc.rightsPublisher Policy
dc.sourcePMC
dc.subjectAdaptive immunity
dc.subjectBNT162 vaccine
dc.subjectCD8-Positive T-Lymphocytes
dc.subjectmRNA vaccines
dc.titleMechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine
dc.typeArticle
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
nihms-1782102.pdf
Size:
4.98 MB
Format:
Adobe Portable Document Format
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.99 KB
Format:
Item-specific license agreed upon to submission
Description: