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The BNT162b2 mRNA Vaccine Against SARS-CoV-2 Reprograms Both Adaptive and Innate Immune Responses

29 Pages Posted: 4 May 2021 Publication Status: Review Complete

See all articles by F. Konstantin Föhse

F. Konstantin Föhse

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Büsranur Geckin

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Gijs J. Overheul

Radboud University Nijmegen - Radboud Institute of Molecular Life Sciences (RIMLS)

Josephine van de Maat

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Gizem Kilic

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Ozlem Bulut

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Helga Dijkstra

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Heidi Lemmers

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

S. Andrei Sarlea

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Maartje Reijnders

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Jacobien Hoogerwerf

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Jaap ten Oever

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Elles Simonetti

Radboud University Nijmegen - Radboud Institute of Molecular Life Sciences (RIMLS)

Frank L. van de Veerdonk

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI); Radboud University Nijmegen - Department of Internal Medicine

Leo A.B. Joosten

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Bart L. Haagmans

Erasmus Medical Center - Viroscience Department

reinout van Crevel

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Yang Li

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Ronald P. van Rij

Radboud University Nijmegen - Radboud Institute of Molecular Life Sciences (RIMLS)

Corine Geurtsvan Kessel

Erasmus University Rotterdam (EUR) - Department of Viroscience

Marien I. de Jonge

Radboud University Nijmegen - Radboud University Medical Center

Jorge Domínguez-Andrés

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Mihai G. Netea

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI); Radboud University Nijmegen - Department of Internal Medicine

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Abstract

SummaryThe mRNA-based BNT162b2 vaccine from Pfizer/BioNTech was the first registered COVID-19 vaccine and has been shown to be up to 95% effective in preventing SARS-CoV-2 infections. Little is known about the broad effects of the new class of mRNA vaccines, especially whether they have combined effects on innate and adaptive immune responses. Here we confirmed that BNT162b2 vaccination of healthy individuals induced effective humoral and cellular immunity against several SARS-CoV-2 variants. Interestingly, however, the BNT162b2 vaccine also modulated the production of inflammatory cytokines by innate immune cells upon stimulation with both specific (SARS-CoV-2) and non-specific (viral, fungal and bacterial) stimuli. The response of innate immune cells to TLR4 and TLR7/8 ligands was lower after BNT162b2 vaccination, while fungi-induced cytokine responses were stronger. In conclusion, the mRNA BNT162b2 vaccine induces complex functional reprogramming of innate immune responses, which should be considered in the development and use of this new class of vaccines.

Keywords: COVID-19, coronaviruses, mRNA vaccines, trained immunity, innate immune tolerance

Suggested Citation

Föhse, F. Konstantin and Geckin, Büsranur and Overheul, Gijs J. and van de Maat, Josephine and Kilic, Gizem and Bulut, Ozlem and Dijkstra, Helga and Lemmers, Heidi and Sarlea, S. Andrei and Reijnders, Maartje and Hoogerwerf, Jacobien and ten Oever, Jaap and Simonetti, Elles and van de Veerdonk, Frank L. and Joosten, Leo A.B. and Haagmans, Bart L. and van Crevel, reinout and Li, Yang and van Rij, Ronald P. and Geurtsvan Kessel, Corine and de Jonge, Marien I. and Domínguez-Andrés, Jorge and Netea, Mihai G. and Netea, Mihai G., The BNT162b2 mRNA Vaccine Against SARS-CoV-2 Reprograms Both Adaptive and Innate Immune Responses. Available at SSRN: https://ssrn.com/abstract=3839624 or http://dx.doi.org/10.2139/ssrn.3839624
This version of the paper has not been formally peer reviewed.

F. Konstantin Föhse

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI) ( email )

Nijmegen
Netherlands

Büsranur Geckin

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI) ( email )

Nijmegen
Netherlands

Gijs J. Overheul

Radboud University Nijmegen - Radboud Institute of Molecular Life Sciences (RIMLS) ( email )

6525 GA Nijmegen
Netherlands

Josephine Van de Maat

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI) ( email )

Nijmegen
Netherlands

Gizem Kilic

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI) ( email )

Nijmegen
Netherlands

Ozlem Bulut

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI) ( email )

Nijmegen
Netherlands

Helga Dijkstra

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI) ( email )

Nijmegen
Netherlands

Heidi Lemmers

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI) ( email )

Nijmegen
Netherlands

S. Andrei Sarlea

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI) ( email )

Nijmegen
Netherlands

Maartje Reijnders

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI) ( email )

Nijmegen
Netherlands

Jacobien Hoogerwerf

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Nijmegen
Netherlands

Jaap Ten Oever

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI) ( email )

Nijmegen
Netherlands

Elles Simonetti

Radboud University Nijmegen - Radboud Institute of Molecular Life Sciences (RIMLS) ( email )

6525 GA Nijmegen
Netherlands

Frank L. Van de Veerdonk

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI) ( email )

Nijmegen
Netherlands

Radboud University Nijmegen - Department of Internal Medicine ( email )

Nijmegen
Netherlands

Leo A.B. Joosten

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI) ( email )

Nijmegen
Netherlands

Bart L. Haagmans

Erasmus Medical Center - Viroscience Department ( email )

Netherlands

Reinout Van Crevel

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI) ( email )

Nijmegen
Netherlands

Yang Li

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Nijmegen
Netherlands

Ronald P. Van Rij

Radboud University Nijmegen - Radboud Institute of Molecular Life Sciences (RIMLS) ( email )

6525 GA Nijmegen
Netherlands

Corine Geurtsvan Kessel

Erasmus University Rotterdam (EUR) - Department of Viroscience

Netherlands

Marien I. De Jonge

Radboud University Nijmegen - Radboud University Medical Center ( email )

Geert Grooteplein Zuid 10
Nijmegen
Netherlands

Jorge Domínguez-Andrés

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI) ( email )

Nijmegen
Netherlands

Mihai G. Netea (Contact Author)

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Nijmegen
Netherlands

Radboud University Nijmegen - Department of Internal Medicine ( email )

Nijmegen
Netherlands

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