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

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. 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; Kai Wu; Carole Henry; Kapil Bahl; Dario Garcia-Dominguez; Ling Zhi Ma; Isabella Renzi; Wing Pui Kong; Stephen D. Schmidt; Lingshu Wang; Yi Zhang; Emily Phung; Lauren A. Chang; Rebecca J. Loomis; Nedim Emil Altaras; Elisabeth Narayanan; Mihir Metkar; Vlad Presnyak; Cuiping Liu; Mark K. Louder; Wei Shi; Kwanyee Leung; Eun Sung Yang; Ande West; Kendra L. Gully; Laura J. Stevens; Nianshuang Wang; Daniel Wrapp; Nicole A. Doria-Rose; Guillaume Stewart-Jones; Hamilton Bennett; Gabriela S. Alvarado; 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

doi:10.1038/s41586-020-2622-0

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

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. 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

Kai Wu, Carole Henry, Kapil Bahl, Dario Garcia-Dominguez, Ling Zhi Ma, Isabella Renzi, Wing Pui Kong, Stephen D. Schmidt, Lingshu Wang, Yi Zhang, Emily Phung, Lauren A. Chang, Rebecca J. Loomis, Nedim Emil Altaras, Elisabeth Narayanan, Mihir Metkar, Vlad Presnyak, Cuiping Liu, Mark K. Louder, Wei Shi, Kwanyee Leung, Eun Sung Yang, Ande West, Kendra L. Gully, Laura J. Stevens, Nianshuang Wang, Daniel Wrapp, Nicole A. Doria-Rose, Guillaume Stewart-Jones, Hamilton Bennett, Gabriela S. Alvarado, 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

Research output: Contribution to journal › Article › peer-review

1347 Scopus citations

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.

Original language	English
Pages (from-to)	567-571
Number of pages	5
Journal	Nature
Volume	586
Issue number	7830
DOIs	https://doi.org/10.1038/s41586-020-2622-0
State	Published - 22 Oct 2020
Externally published	Yes

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10.1038/s41586-020-2622-0

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Corbett, K. S., Edwards, D. K., Leist, S. R., Abiona, O. M., Boyoglu-Barnum, S., Gillespie, R. A., Himansu, S., Schäfer, A., Ziwawo, C. T., DiPiazza, A. T., Dinnon, K. H., Elbashir, S. M., Shaw, C. A., Woods, A., Fritch, E. J., Martinez, D. R., Bock, K. W., Minai, M., Nagata, B. M., ... Graham, B. S. (2020). SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature, 586(7830), 567-571. https://doi.org/10.1038/s41586-020-2622-0

@article{3b22adaa53454a619a404d236de1a82c,

title = "SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness",

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.",

author = "Corbett, \{Kizzmekia S.\} and Edwards, \{Darin K.\} and Leist, \{Sarah R.\} and Abiona, \{Olubukola M.\} and Seyhan Boyoglu-Barnum and Gillespie, \{Rebecca A.\} and Sunny Himansu and Alexandra Sch{\"a}fer and Ziwawo, \{Cynthia T.\} and DiPiazza, \{Anthony T.\} and Dinnon, \{Kenneth H.\} and Elbashir, \{Sayda M.\} and Shaw, \{Christine A.\} and Angela Woods and Fritch, \{Ethan J.\} and Martinez, \{David R.\} and Bock, \{Kevin W.\} and Mahnaz Minai and Nagata, \{Bianca M.\} and Hutchinson, \{Geoffrey B.\} and Kai Wu and Carole Henry and Kapil Bahl and Dario Garcia-Dominguez and Ma, \{Ling Zhi\} and Isabella Renzi and Kong, \{Wing Pui\} and Schmidt, \{Stephen D.\} and Lingshu Wang and Yi Zhang and Emily Phung and Chang, \{Lauren A.\} and Loomis, \{Rebecca J.\} and Altaras, \{Nedim Emil\} and Elisabeth Narayanan and Mihir Metkar and Vlad Presnyak and Cuiping Liu and Louder, \{Mark K.\} and Wei Shi and Kwanyee Leung and Yang, \{Eun Sung\} and Ande West and Gully, \{Kendra L.\} and Stevens, \{Laura J.\} and Nianshuang Wang and Daniel Wrapp and Doria-Rose, \{Nicole A.\} and Guillaume Stewart-Jones and Hamilton Bennett and Alvarado, \{Gabriela S.\} and Nason, \{Martha C.\} and Ruckwardt, \{Tracy J.\} and McLellan, \{Jason S.\} and Denison, \{Mark R.\} and Chappell, \{James D.\} and Moore, \{Ian N.\} and Morabito, \{Kaitlyn M.\} and Mascola, \{John R.\} and Baric, \{Ralph S.\} and Andrea Carfi and Graham, \{Barney S.\}",

note = "Publisher Copyright: {\textcopyright} 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.",

year = "2020",

month = oct,

day = "22",

doi = "10.1038/s41586-020-2622-0",

language = "English",

volume = "586",

pages = "567--571",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7830",

}

Corbett, KS, Edwards, DK, Leist, SR, Abiona, OM, Boyoglu-Barnum, S, Gillespie, RA, Himansu, S, Schäfer, A, Ziwawo, CT, DiPiazza, AT, Dinnon, KH, Elbashir, SM, Shaw, CA, Woods, A, Fritch, EJ, Martinez, DR, Bock, KW, Minai, M, Nagata, BM, Hutchinson, GB, Wu, K, Henry, C, Bahl, K, Garcia-Dominguez, D, Ma, LZ, Renzi, I, Kong, WP, Schmidt, SD, Wang, L, Zhang, Y, Phung, E, Chang, LA, Loomis, RJ, Altaras, NE, Narayanan, E, Metkar, M, Presnyak, V, Liu, C, Louder, MK, Shi, W, Leung, K, Yang, ES, West, A, Gully, KL, Stevens, LJ, Wang, N, Wrapp, D, Doria-Rose, NA, Stewart-Jones, G, Bennett, H, Alvarado, GS, Nason, MC, Ruckwardt, TJ, McLellan, JS, Denison, MR, Chappell, JD, Moore, IN, Morabito, KM, Mascola, JR, Baric, RS, Carfi, A & Graham, BS 2020, 'SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness', Nature, vol. 586, no. 7830, pp. 567-571. https://doi.org/10.1038/s41586-020-2622-0

TY - JOUR

T1 - SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness

AU - Corbett, Kizzmekia S.

AU - Edwards, Darin K.

AU - Leist, Sarah R.

AU - Abiona, Olubukola M.

AU - Boyoglu-Barnum, Seyhan

AU - Gillespie, Rebecca A.

AU - Himansu, Sunny

AU - Schäfer, Alexandra

AU - Ziwawo, Cynthia T.

AU - DiPiazza, Anthony T.

AU - Dinnon, Kenneth H.

AU - Elbashir, Sayda M.

AU - Shaw, Christine A.

AU - Woods, Angela

AU - Fritch, Ethan J.

AU - Martinez, David R.

AU - Bock, Kevin W.

AU - Minai, Mahnaz

AU - Nagata, Bianca M.

AU - Hutchinson, Geoffrey B.

AU - Wu, Kai

AU - Henry, Carole

AU - Bahl, Kapil

AU - Garcia-Dominguez, Dario

AU - Ma, Ling Zhi

AU - Renzi, Isabella

AU - Kong, Wing Pui

AU - Schmidt, Stephen D.

AU - Wang, Lingshu

AU - Zhang, Yi

AU - Phung, Emily

AU - Chang, Lauren A.

AU - Loomis, Rebecca J.

AU - Altaras, Nedim Emil

AU - Narayanan, Elisabeth

AU - Metkar, Mihir

AU - Presnyak, Vlad

AU - Liu, Cuiping

AU - Louder, Mark K.

AU - Shi, Wei

AU - Leung, Kwanyee

AU - Yang, Eun Sung

AU - West, Ande

AU - Gully, Kendra L.

AU - Stevens, Laura J.

AU - Wang, Nianshuang

AU - Wrapp, Daniel

AU - Doria-Rose, Nicole A.

AU - Stewart-Jones, Guillaume

AU - Bennett, Hamilton

AU - Alvarado, Gabriela S.

AU - Nason, Martha C.

AU - Ruckwardt, Tracy J.

AU - McLellan, Jason S.

AU - Denison, Mark R.

AU - Chappell, James D.

AU - Moore, Ian N.

AU - Morabito, Kaitlyn M.

AU - Mascola, John R.

AU - Baric, Ralph S.

AU - Carfi, Andrea

AU - Graham, Barney S.

PY - 2020/10/22

Y1 - 2020/10/22

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85088965235

U2 - 10.1038/s41586-020-2622-0

DO - 10.1038/s41586-020-2622-0

M3 - Article

C2 - 32756549

AN - SCOPUS:85088965235

SN - 0028-0836

VL - 586

SP - 567

EP - 571

JO - Nature

JF - Nature

IS - 7830

ER -

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

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