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SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness

Author

Listed:
  • Kizzmekia S. Corbett

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Darin K. Edwards

    (Moderna Inc)

  • Sarah R. Leist

    (University of North Carolina at Chapel Hill)

  • Olubukola M. Abiona

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Seyhan Boyoglu-Barnum

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Rebecca A. Gillespie

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Sunny Himansu

    (Moderna Inc)

  • Alexandra Schäfer

    (University of North Carolina at Chapel Hill)

  • Cynthia T. Ziwawo

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Anthony T. DiPiazza

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Kenneth H. Dinnon

    (University of North Carolina at Chapel Hill)

  • Sayda M. Elbashir

    (Moderna Inc)

  • Christine A. Shaw

    (Moderna Inc)

  • Angela Woods

    (Moderna Inc)

  • Ethan J. Fritch

    (University of North Carolina at Chapel Hill)

  • David R. Martinez

    (University of North Carolina at Chapel Hill)

  • Kevin W. Bock

    (National Institutes of Health)

  • Mahnaz Minai

    (National Institutes of Health)

  • Bianca M. Nagata

    (National Institutes of Health)

  • Geoffrey B. Hutchinson

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Kai Wu

    (Moderna Inc)

  • Carole Henry

    (Moderna Inc)

  • Kapil Bahl

    (Moderna Inc)

  • Dario Garcia-Dominguez

    (Moderna Inc)

  • LingZhi Ma

    (Moderna Inc)

  • Isabella Renzi

    (Moderna Inc)

  • Wing-Pui Kong

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Stephen D. Schmidt

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Lingshu Wang

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Yi Zhang

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Emily Phung

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
    George Washington University)

  • Lauren A. Chang

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Rebecca J. Loomis

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Nedim Emil Altaras

    (Moderna Inc)

  • Elisabeth Narayanan

    (Moderna Inc)

  • Mihir Metkar

    (Moderna Inc)

  • Vlad Presnyak

    (Moderna Inc)

  • Cuiping Liu

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Mark K. Louder

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Wei Shi

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Kwanyee Leung

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Eun Sung Yang

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Ande West

    (University of North Carolina at Chapel Hill)

  • Kendra L. Gully

    (University of North Carolina at Chapel Hill)

  • Laura J. Stevens

    (Vanderbilt University Medical Center)

  • Nianshuang Wang

    (University of Texas at Austin)

  • Daniel Wrapp

    (University of Texas at Austin)

  • Nicole A. Doria-Rose

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Guillaume Stewart-Jones

    (Moderna Inc)

  • Hamilton Bennett

    (Moderna Inc)

  • Gabriela S. Alvarado

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Martha C. Nason

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Tracy J. Ruckwardt

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Jason S. McLellan

    (University of Texas at Austin)

  • Mark R. Denison

    (Vanderbilt University Medical Center)

  • James D. Chappell

    (Vanderbilt University Medical Center)

  • Ian N. Moore

    (National Institutes of Health)

  • Kaitlyn M. Morabito

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • John R. Mascola

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Ralph S. Baric

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Andrea Carfi

    (Moderna Inc)

  • Barney S. Graham

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

Abstract

A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the coronavirus disease 2019 (COVID-19) global pandemic. Structural studies have led to the development of mutations that stabilize Betacoronavirus spike proteins in the prefusion state, improving their expression and increasing immunogenicity1. This principle has been applied to design mRNA-1273, an mRNA vaccine that encodes a SARS-CoV-2 spike protein that is stabilized in the prefusion conformation. Here we show that mRNA-1273 induces potent neutralizing antibody responses to both wild-type (D614) and D614G mutant2 SARS-CoV-2 as well as CD8+ T cell responses, and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a phase III trial to evaluate its efficacy.

Suggested Citation

  • Kizzmekia S. Corbett & Darin K. Edwards & Sarah R. Leist & Olubukola M. Abiona & Seyhan Boyoglu-Barnum & Rebecca A. Gillespie & Sunny Himansu & Alexandra Schäfer & Cynthia T. Ziwawo & Anthony T. DiPia, 2020. "SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness," Nature, Nature, vol. 586(7830), pages 567-571, October.
    • Handle: RePEc:nat:nature:v:586:y:2020:i:7830:d:10.1038_s41586-020-2622-0
    DOI: 10.1038/s41586-020-2622-0
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    Cited by:

    1. Wenjun Zhu & Ting Wei & Yuchun Xu & Qiutong Jin & Yu Chao & Jiaqi Lu & Jun Xu & Jiafei Zhu & Xiaoying Yan & Muchao Chen & Qian Chen & Zhuang Liu, 2024. "Non-invasive transdermal delivery of biomacromolecules with fluorocarbon-modified chitosan for melanoma immunotherapy and viral vaccines," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Rafael R. G. Machado & Jordyn L. Walker & Dionna Scharton & Grace H. Rafael & Brooke M. Mitchell & Rachel A. Reyna & William M. Souza & Jianying Liu & David H. Walker & Jessica A. Plante & Kenneth S. , 2023. "Immunogenicity and efficacy of vaccine boosters against SARS-CoV-2 Omicron subvariant BA.5 in male Syrian hamsters," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. David Chmielewski & Eric A. Wilson & Grigore Pintilie & Peng Zhao & Muyuan Chen & Michael F. Schmid & Graham Simmons & Lance Wells & Jing Jin & Abhishek Singharoy & Wah Chiu, 2023. "Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Neeltje van Doremalen & Jonathan E. Schulz & Danielle R. Adney & Taylor A. Saturday & Robert J. Fischer & Claude Kwe Yinda & Nazia Thakur & Joseph Newman & Marta Ulaszewska & Sandra Belij-Rammerstorfe, 2022. "ChAdOx1 nCoV-19 (AZD1222) or nCoV-19-Beta (AZD2816) protect Syrian hamsters against Beta Delta and Omicron variants," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. Mark P. Khurana & Jacob Curran-Sebastian & Neil Scheidwasser & Christian Morgenstern & Morten Rasmussen & Jannik Fonager & Marc Stegger & Man-Hung Eric Tang & Jonas L. Juul & Leandro Andrés Escobar-He, 2024. "High-resolution epidemiological landscape from ~290,000 SARS-CoV-2 genomes from Denmark," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    6. Zhenhao Fang & Lei Peng & Renata Filler & Kazushi Suzuki & Andrew McNamara & Qianqian Lin & Paul A. Renauer & Luojia Yang & Bridget Menasche & Angie Sanchez & Ping Ren & Qiancheng Xiong & Madison Stri, 2022. "Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2," Nature Communications, Nature, vol. 13(1), pages 1-12, 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. Geoffrey B. Hutchinson & Olubukola M. Abiona & Cynthia T. Ziwawo & Anne P. Werner & Daniel Ellis & Yaroslav Tsybovsky & Sarah R. Leist & Charis Palandjian & Ande West & Ethan J. Fritch & Nianshuang Wa, 2023. "Nanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive antibody response against diverse coronavirus subgenera," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    9. Kathrin Leppek & Gun Woo Byeon & Wipapat Kladwang & Hannah K. Wayment-Steele & Craig H. Kerr & Adele F. Xu & Do Soon Kim & Ved V. Topkar & Christian Choe & Daphna Rothschild & Gerald C. Tiu & Roger We, 2022. "Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    10. Jimin Lee & Cameron Stewart & Alexandra Schäfer & Elizabeth M. Leaf & Young-Jun Park & Daniel Asarnow & John M. Powers & Catherine Treichel & Kaitlin R. Sprouse & Davide Corti & Ralph Baric & Neil P. , 2024. "A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    11. Patrick O. Byrne & Brian E. Fisher & David R. Ambrozak & Elizabeth G. Blade & Yaroslav Tsybovsky & Barney S. Graham & Jason S. McLellan & Rebecca J. Loomis, 2023. "Structural basis for antibody recognition of vulnerable epitopes on Nipah virus F protein," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    12. Carlos Ávila-Nieto & Júlia Vergara-Alert & Pep Amengual-Rigo & Erola Ainsua-Enrich & Marco Brustolin & María Luisa Rodríguez de la Concepción & Núria Pedreño-Lopez & Jordi Rodon & Victor Urrea & Edwar, 2024. "Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    13. Zhangli Su & Ida Monshaugen & Briana Wilson & Fengbin Wang & Arne Klungland & Rune Ougland & Anindya Dutta, 2022. "TRMT6/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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