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SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness

Kizzmekia S. Corbett, Darin Edwards, Sarah R. Leist, Olubukola M. Abiona, Seyhan Boyoglu-Barnum, Rebecca A. Gillespie, Sunny Himansu, Alexandra Schäfer, Cynthia T. Ziwawo, Anthony T. DiPiazza, Kenneth H. Dinnon, Sayda M. Elbashir, Christine A. Shaw, Angela Woods, Ethan J. Fritch, David R. Martinez, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Geoffrey B. Hutchinson, Kapil Bahl, Dario Garcia-Dominguez, LingZhi Ma, Isabella Renzi, Wing-Pui Kong, Stephen D. Schmidt, Lingshu Wang, Yi Zhang, Laura J. Stevens, Emily Phung, Lauren A. Chang, Rebecca J. Loomis, Nedim Emil Altaras, Elisabeth Narayanan, Mihir Metkar, Vlad Presnyak, Catherine Liu, Mark K. Louder, Wei Shi, Kwanyee Leung, Eun Sung Yang, Ande West, Kendra L. Gully, Nianshuang Wang, Daniel Wrapp, Nicole A. Doria-Rose, Guillaume Stewart-Jones, Hamilton Bennett, Martha C. Nason, Tracy J. Ruckwardt, Jason S. McLellan, Mark R. Denison, James D. Chappell, Ian N. Moore, Kaitlyn M. Morabito, John R. Mascola, Ralph S. Baric, Andrea Carfi, View ORCID ProfileBarney S. Graham
doi: https://doi.org/10.1101/2020.06.11.145920
Kizzmekia S. Corbett
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Darin Edwards
2Moderna Inc., Cambridge, MA, 02139; United States of America
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Sarah R. Leist
3Department of Epidemiology; University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America
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Olubukola M. Abiona
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Seyhan Boyoglu-Barnum
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Rebecca A. Gillespie
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Sunny Himansu
2Moderna Inc., Cambridge, MA, 02139; United States of America
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Alexandra Schäfer
3Department of Epidemiology; University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America
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Cynthia T. Ziwawo
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Anthony T. DiPiazza
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Kenneth H. Dinnon
3Department of Epidemiology; University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America
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Sayda M. Elbashir
2Moderna Inc., Cambridge, MA, 02139; United States of America
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Christine A. Shaw
2Moderna Inc., Cambridge, MA, 02139; United States of America
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Angela Woods
2Moderna Inc., Cambridge, MA, 02139; United States of America
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Ethan J. Fritch
4Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America
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David R. Martinez
3Department of Epidemiology; University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America
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Kevin W. Bock
5National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Mahnaz Minai
5National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Bianca M. Nagata
5National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Geoffrey B. Hutchinson
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Kapil Bahl
2Moderna Inc., Cambridge, MA, 02139; United States of America
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Dario Garcia-Dominguez
2Moderna Inc., Cambridge, MA, 02139; United States of America
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LingZhi Ma
2Moderna Inc., Cambridge, MA, 02139; United States of America
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Isabella Renzi
2Moderna Inc., Cambridge, MA, 02139; United States of America
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Wing-Pui Kong
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Stephen D. Schmidt
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Lingshu Wang
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Yi Zhang
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Laura J. Stevens
6Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, 37212; United States of America
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Emily Phung
7Institute for Biomedical Sciences, George Washington University, Washington, DC 20052, United States of America
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Lauren A. Chang
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Rebecca J. Loomis
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Nedim Emil Altaras
2Moderna Inc., Cambridge, MA, 02139; United States of America
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Elisabeth Narayanan
2Moderna Inc., Cambridge, MA, 02139; United States of America
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Mihir Metkar
2Moderna Inc., Cambridge, MA, 02139; United States of America
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Vlad Presnyak
2Moderna Inc., Cambridge, MA, 02139; United States of America
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Catherine Liu
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Mark K. Louder
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Wei Shi
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Kwanyee Leung
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Eun Sung Yang
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Ande West
3Department of Epidemiology; University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America
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Kendra L. Gully
3Department of Epidemiology; University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America
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Nianshuang Wang
8Department of Molecular Biosciences; University of Texas at Austin; Austin, Texas, 78712; United States of America
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Daniel Wrapp
8Department of Molecular Biosciences; University of Texas at Austin; Austin, Texas, 78712; United States of America
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Nicole A. Doria-Rose
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Guillaume Stewart-Jones
2Moderna Inc., Cambridge, MA, 02139; United States of America
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Hamilton Bennett
2Moderna Inc., Cambridge, MA, 02139; United States of America
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Martha C. Nason
9Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Tracy J. Ruckwardt
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Jason S. McLellan
8Department of Molecular Biosciences; University of Texas at Austin; Austin, Texas, 78712; United States of America
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Mark R. Denison
6Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, 37212; United States of America
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James D. Chappell
6Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, 37212; United States of America
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Ian N. Moore
5National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Kaitlyn M. Morabito
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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John R. Mascola
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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Ralph S. Baric
3Department of Epidemiology; University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America
4Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill; Chapel Hill, North Carolina, 27599; United States of America
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Andrea Carfi
2Moderna Inc., Cambridge, MA, 02139; United States of America
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  • For correspondence: bgraham@nih.gov Andrea.Carfi@modernatx.com
Barney S. Graham
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America
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  • ORCID record for Barney S. Graham
  • For correspondence: bgraham@nih.gov Andrea.Carfi@modernatx.com
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Summary

A SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of betacoronavirus spike proteins. Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here, we show that mRNA-1273 induces both potent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a Phase 2 clinical trial with a trajectory towards Phase 3 efficacy evaluation.

Competing Interest Statement

K.S.C., N.W., J.S.M., and B.S.G. are inventors on International Patent Application No. WO/2018/081318 entitled Prefusion Coronavirus Spike Proteins and Their Use. K.S.C., O.M.A., G.B.H., N.W., D.W., J.S.M, and B.S.G. are inventors on US Patent Application No. 62/972,886 entitled 2019-nCoV Vaccine. R.S.B. filed an invention report for the SARS-CoV-2 MA virus (UNC ref. #18752).

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness
Kizzmekia S. Corbett, Darin Edwards, Sarah R. Leist, Olubukola M. Abiona, Seyhan Boyoglu-Barnum, Rebecca A. Gillespie, Sunny Himansu, Alexandra Schäfer, Cynthia T. Ziwawo, Anthony T. DiPiazza, Kenneth H. Dinnon, Sayda M. Elbashir, Christine A. Shaw, Angela Woods, Ethan J. Fritch, David R. Martinez, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Geoffrey B. Hutchinson, Kapil Bahl, Dario Garcia-Dominguez, LingZhi Ma, Isabella Renzi, Wing-Pui Kong, Stephen D. Schmidt, Lingshu Wang, Yi Zhang, Laura J. Stevens, Emily Phung, Lauren A. Chang, Rebecca J. Loomis, Nedim Emil Altaras, Elisabeth Narayanan, Mihir Metkar, Vlad Presnyak, Catherine Liu, Mark K. Louder, Wei Shi, Kwanyee Leung, Eun Sung Yang, Ande West, Kendra L. Gully, Nianshuang Wang, Daniel Wrapp, Nicole A. Doria-Rose, Guillaume Stewart-Jones, Hamilton Bennett, Martha C. Nason, Tracy J. Ruckwardt, Jason S. McLellan, Mark R. Denison, James D. Chappell, Ian N. Moore, Kaitlyn M. Morabito, John R. Mascola, Ralph S. Baric, Andrea Carfi, Barney S. Graham
bioRxiv 2020.06.11.145920; doi: https://doi.org/10.1101/2020.06.11.145920
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SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness
Kizzmekia S. Corbett, Darin Edwards, Sarah R. Leist, Olubukola M. Abiona, Seyhan Boyoglu-Barnum, Rebecca A. Gillespie, Sunny Himansu, Alexandra Schäfer, Cynthia T. Ziwawo, Anthony T. DiPiazza, Kenneth H. Dinnon, Sayda M. Elbashir, Christine A. Shaw, Angela Woods, Ethan J. Fritch, David R. Martinez, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Geoffrey B. Hutchinson, Kapil Bahl, Dario Garcia-Dominguez, LingZhi Ma, Isabella Renzi, Wing-Pui Kong, Stephen D. Schmidt, Lingshu Wang, Yi Zhang, Laura J. Stevens, Emily Phung, Lauren A. Chang, Rebecca J. Loomis, Nedim Emil Altaras, Elisabeth Narayanan, Mihir Metkar, Vlad Presnyak, Catherine Liu, Mark K. Louder, Wei Shi, Kwanyee Leung, Eun Sung Yang, Ande West, Kendra L. Gully, Nianshuang Wang, Daniel Wrapp, Nicole A. Doria-Rose, Guillaume Stewart-Jones, Hamilton Bennett, Martha C. Nason, Tracy J. Ruckwardt, Jason S. McLellan, Mark R. Denison, James D. Chappell, Ian N. Moore, Kaitlyn M. Morabito, John R. Mascola, Ralph S. Baric, Andrea Carfi, Barney S. Graham
bioRxiv 2020.06.11.145920; doi: https://doi.org/10.1101/2020.06.11.145920

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