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Systems vaccinology of the BNT162b2 mRNA vaccine in humans

Author

Listed:
  • Prabhu S. Arunachalam

    (Stanford University)

  • Madeleine K. D. Scott

    (Stanford University
    Stanford University School of Medicine, Stanford University)

  • Thomas Hagan

    (Cincinnati Children’s Hospital Medical Center
    University of Cincinnati College of Medicine)

  • 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
    Stanford University School of Medicine, Stanford University)

  • Allan Feng

    (Stanford University
    Stanford University School of Medicine, Stanford University)

  • Shaurya Dhingra

    (Stanford University
    Stanford University School of Medicine, 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
    Emory University School of Medicine)

  • Holden T. Maecker

    (Stanford University)

  • Scott D. Boyd

    (Sean N. Parker Center for Allergy and Asthma Research, Stanford University
    Stanford University School of Medicine, Stanford University)

  • Mark M. Davis

    (Stanford University
    Stanford University School of Medicine, Stanford University
    Stanford University School of Medicine, Stanford University)

  • Paul J. Utz

    (Stanford University
    Stanford University School of Medicine, Stanford University)

  • Mehul S. Suthar

    (Yerkes National Primate Research Center)

  • Purvesh Khatri

    (Stanford University
    Stanford University School of Medicine, Stanford University)

  • Kari C. Nadeau

    (Sean N. Parker Center for Allergy and Asthma Research, Stanford University
    Stanford University
    Stanford University School of Medicine, Stanford University)

  • Bali Pulendran

    (Stanford University
    Stanford University School of Medicine, Stanford University
    Stanford University School of Medicine, Stanford University)

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.

Suggested Citation

  • 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 &, 2021. "Systems vaccinology of the BNT162b2 mRNA vaccine in humans," Nature, Nature, vol. 596(7872), pages 410-416, August.
  • Handle: RePEc:nat:nature:v:596:y:2021:i:7872:d:10.1038_s41586-021-03791-x
    DOI: 10.1038/s41586-021-03791-x
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    Cited by:

    1. Eva M. Stevenson & Sandra Terry & Dennis Copertino & Louise Leyre & Ali Danesh & Jared Weiler & Adam R. Ward & Pragya Khadka & Evan McNeil & Kevin Bernard & Itzayana G. Miller & Grant B. Ellsworth & C, 2022. "SARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8+ T-cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Kevin J. Kramer & Erin M. Wilfong & Kelsey Voss & Sierra M. Barone & Andrea R. Shiakolas & Nagarajan Raju & Caroline E. Roe & Naveenchandra Suryadevara & Lauren M. Walker & Steven C. Wall & Ariana Pau, 2022. "Single-cell profiling of the antigen-specific response to BNT162b2 SARS-CoV-2 RNA vaccine," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    3. Chaim A. Schramm & Damee Moon & Lowrey Peyton & Noemia S. Lima & Christian Wake & Kristin L. Boswell & Amy R. Henry & Farida Laboune & David Ambrozak & Samuel W. Darko & I-Ting Teng & Kathryn E. Fould, 2023. "Interaction dynamics between innate and adaptive immune cells responding to SARS-CoV-2 vaccination in non-human primates," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Tomohiro Takano & Takashi Sato & Ryutaro Kotaki & Saya Moriyama & Shuetsu Fukushi & Masahiro Shinoda & Kiyomi Kabasawa & Nagashige Shimada & Mio Kousaka & Yu Adachi & Taishi Onodera & Kazutaka Terahar, 2023. "Heterologous SARS-CoV-2 spike protein booster elicits durable and broad antibody responses against the receptor-binding domain," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Wen Juan Tu & Michelle Melino & Jenny Dunn & Robert D. McCuaig & Helle Bielefeldt-Ohmann & Sofiya Tsimbalyuk & Jade K. Forwood & Taniya Ahuja & John Vandermeide & Xiao Tan & Minh Tran & Quan Nguyen & , 2023. "In vivo inhibition of nuclear ACE2 translocation protects against SARS-CoV-2 replication and lung damage through epigenetic imprinting," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    6. Fredrika Hellgren & Alberto Cagigi & Rodrigo Arcoverde Cerveira & Sebastian Ols & Theresa Kern & Ang Lin & Bengt Eriksson & Michael G. Dodds & Edith Jasny & Kim Schwendt & Conrad Freuling & Thomas Mül, 2023. "Unmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Seongryong Kim & Ji Hyang Jeon & Myeonghwan Kim & Yeji Lee & Yun-Ho Hwang & Myungsun Park & C. Han Li & Taeyoung Lee & Jung-Ah Lee & You-Me Kim & Dokeun Kim & Hyukjin Lee & You-Jin Kim & V. Narry Kim , 2024. "Innate immune responses against mRNA vaccine promote cellular immunity through IFN-β at the injection site," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Andrew P. Hederman & Harini Natarajan & Leo Heyndrickx & Kevin K. Ariën & Joshua A. Wiener & Peter F. Wright & Evan M. Bloch & Aaron A. R. Tobian & Andrew D. Redd & Joel N. Blankson & Amihai Rottenstr, 2023. "SARS-CoV-2 vaccination elicits broad and potent antibody effector functions to variants of concern in vulnerable populations," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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