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

被引:358
作者
Corbett, Kizzmekia S. [1 ]
Edwards, Darin K. [2 ]
Leist, Sarah R. [3 ]
Abiona, Olubukola M. [1 ]
Boyoglu-Barnum, Seyhan [1 ]
Gillespie, Rebecca A. [1 ]
Himansu, Sunny [2 ]
Schafer, Alexandra [3 ]
Ziwawo, Cynthia T. [1 ]
DiPiazza, Anthony T. [1 ]
Dinnon, Kenneth H. [3 ]
Elbashir, Sayda M. [2 ]
Shaw, Christine A. [2 ]
Woods, Angela [2 ]
Fritch, Ethan J. [4 ]
Martinez, David R. [3 ]
Bock, Kevin W. [5 ]
Minai, Mahnaz [5 ]
Nagata, Bianca M. [5 ]
Hutchinson, Geoffrey B. [1 ]
Wu, Kai [2 ]
Henry, Carole [2 ]
Bahl, Kapil
Garcia-Dominguez, Dario [2 ]
Ma, LingZhi [2 ]
Renzi, Isabella [2 ]
Kong, Wing-Pui [1 ]
Schmidt, Stephen D. [1 ]
Wang, Lingshu [1 ]
Zhang, Yi [1 ]
Phung, Emily [1 ,6 ]
Chang, Lauren A. [1 ]
Loomis, Rebecca J. [1 ]
Altaras, Nedim Emil [2 ]
Narayanan, Elisabeth [2 ]
Metkar, Mihir [2 ]
Presnyak, Vlad [2 ]
Liu, Cuiping [1 ]
Louder, Mark K. [1 ]
Shi, Wei [1 ]
Leung, Kwanyee [1 ]
Yang, Eun Sung [1 ]
West, Ande [3 ]
Gully, Kendra L. [3 ]
Stevens, Laura J. [7 ]
Gully, Kendra L. [3 ]
Wang, Nianshuang [8 ]
Wrapp, Daniel [8 ]
Doria-Rose, Nicole A. [1 ]
Stewart-Jones, Guillaume [2 ]
机构
[1] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[2] Moderna Inc, Cambridge, MA USA
[3] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27515 USA
[4] Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27515 USA
[5] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[6] George Washington Univ, Inst Biomed Sci, Washington, DC USA
[7] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA
[8] Univ Texas Austin, Dept Mol Biosci, Austin, TX 78712 USA
[9] NIAID, Biostat Res Branch, Div Clin Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
关键词
MERS-COV; SPIKE; INFLUENZA; IMMUNOGENICITY; PROTECTION; VIRUS; RSV;
D O I
10.1038/s41586-020-2622-0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 immunogenicity(1). 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 mutant(2) 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.
引用
收藏
页码:567 / +
页数:21
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