Systems vaccinology of the BNT162b2 mRNA vaccine in humans

Prabhu S. Arunachalam, Madeleine K. D. Scott, Thomas Hagan, Chunfeng Li, Yupeng Feng, Florian Wimmers, Lilit Grigoryan, Meera Trisal, Venkata Viswanadh Edara, Lilin Lai, Sarah Esther Chang, Allan Feng, Shaurya Dhingra, Mihir Shah, Alexandra S. Lee, Sharon Chinthrajah, Sayantani B. Sindher, Vamsee Mallajosyula, Fei Gao, Natalia Sigal, Sangeeta Kowli, Sheena Gupta, Kathryn Pellegrini, Gregory Tharp, Sofia Maysel-Auslender, Sydney Hamilton, Hadj Aoued, Kevin Hrusovsky, Mark Roskey, Steven E. Bosinger, Holden T. Maecker, Scott D. Boyd, Mark M. Davis, Paul J. Utz, Mehul S. Suthar, Purvesh Khatri (), Kari C. Nadeau () and Bali Pulendran ()
Additional contact information
Prabhu S. Arunachalam: Stanford University
Madeleine K. D. Scott: Stanford University
Thomas Hagan: Cincinnati Children’s Hospital Medical Center
Chunfeng Li: Stanford University
Yupeng Feng: Stanford University
Florian Wimmers: Stanford University
Lilit Grigoryan: Stanford University
Meera Trisal: Stanford University
Venkata Viswanadh Edara: Yerkes National Primate Research Center
Lilin Lai: Yerkes National Primate Research Center
Sarah Esther Chang: Stanford University
Allan Feng: Stanford University
Shaurya Dhingra: Stanford University
Mihir Shah: Sean N. Parker Center for Allergy and Asthma Research, Stanford University
Alexandra S. Lee: Sean N. Parker Center for Allergy and Asthma Research, Stanford University
Sharon Chinthrajah: Sean N. Parker Center for Allergy and Asthma Research, Stanford University
Sayantani B. Sindher: Sean N. Parker Center for Allergy and Asthma Research, Stanford University
Vamsee Mallajosyula: Stanford University
Fei Gao: Stanford University
Natalia Sigal: Stanford University
Sangeeta Kowli: Stanford University
Sheena Gupta: Stanford University
Kathryn Pellegrini: Yerkes National Primate Research Center
Gregory Tharp: Yerkes National Primate Research Center
Sofia Maysel-Auslender: Stanford University
Sydney Hamilton: Yerkes National Primate Research Center
Hadj Aoued: Yerkes National Primate Research Center
Kevin Hrusovsky: Quanterix
Mark Roskey: Quanterix
Steven E. Bosinger: University of Cincinnati College of Medicine
Holden T. Maecker: Stanford University
Scott D. Boyd: Sean N. Parker Center for Allergy and Asthma Research, Stanford University
Mark M. Davis: Stanford University
Paul J. Utz: Stanford University
Mehul S. Suthar: Yerkes National Primate Research Center
Purvesh Khatri: Stanford University
Kari C. Nadeau: Sean N. Parker Center for Allergy and Asthma Research, Stanford University
Bali Pulendran: Stanford University

Nature, 2021, vol. 596, issue 7872, 410-416

Abstract: Abstract The emergency use authorization of two mRNA vaccines in less than a year from the emergence of SARS-CoV-2 represents a landmark in vaccinology1,2. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers who were vaccinated with the Pfizer–BioNTech mRNA vaccine (BNT162b2). Vaccination resulted in the robust production of neutralizing antibodies against the wild-type SARS-CoV-2 (derived from 2019-nCOV/USA_WA1/2020) and, to a lesser extent, the B.1.351 strain, as well as significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. Booster vaccination stimulated a notably enhanced innate immune response as compared to primary vaccination, evidenced by (1) a greater frequency of CD14+CD16+ inflammatory monocytes; (2) a higher concentration of plasma IFNγ; and (3) a transcriptional signature of innate antiviral immunity. Consistent with these observations, our single-cell transcriptomics analysis demonstrated an approximately 100-fold increase in the frequency of a myeloid cell cluster enriched in interferon-response transcription factors and reduced in AP-1 transcription factors, after secondary immunization. Finally, we identified distinct innate pathways associated with CD8 T cell and neutralizing antibody responses, and show that a monocyte-related signature correlates with the neutralizing antibody response against the B.1.351 variant. Collectively, these data provide insights into the immune responses induced by mRNA vaccination and demonstrate its capacity to prime the innate immune system to mount a more potent response after booster immunization.

Date: 2021
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DOI: 10.1038/s41586-021-03791-x

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