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

• Published in: Nature (London) Vol. 586; no. 7830; pp. 567 - 571
• Main Authors: Corbett, Kizzmekia S., Edwards, Darin K., Leist, Sarah R., Abiona, Olubukola M., Boyoglu-Barnum, Seyhan, Gillespie, Rebecca A., Himansu, Sunny, Schäfer, Alexandra, Ziwawo, Cynthia T., DiPiazza, Anthony T., Dinnon, Kenneth H., Elbashir, Sayda M., Shaw, Christine A., Woods, Angela, Fritch, Ethan J., Martinez, David R., Bock, Kevin W., Minai, Mahnaz, Nagata, Bianca M., Hutchinson, Geoffrey B., Wu, Kai, Henry, Carole, Bahl, Kapil, Garcia-Dominguez, Dario, Ma, LingZhi, Renzi, Isabella, Kong, Wing-Pui, Schmidt, Stephen D., Wang, Lingshu, Zhang, Yi, Phung, Emily, Chang, Lauren A., Loomis, Rebecca J., Altaras, Nedim Emil, Narayanan, Elisabeth, Metkar, Mihir, Presnyak, Vlad, Liu, Cuiping, Louder, Mark K., Shi, Wei, Leung, Kwanyee, Yang, Eun Sung, West, Ande, Gully, Kendra L., Stevens, Laura J., Wang, Nianshuang, Wrapp, Daniel, Doria-Rose, Nicole A., Stewart-Jones, Guillaume, Bennett, Hamilton, Alvarado, Gabriela S., Nason, Martha C., Ruckwardt, Tracy J., McLellan, Jason S., Denison, Mark R., Chappell, James D., Moore, Ian N., Morabito, Kaitlyn M., Mascola, John R., Baric, Ralph S., Carfi, Andrea, Graham, Barney S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.10.2020; Nature Publishing Group
• Subjects: 13/106; 13/109; 13/21; 13/31; 13/51; 2019-nCoV Vaccine mRNA-1273; 631/250/255/2514; 631/250/590/2293; 631/326/596/4130; 64/60; 82/51; 82/83; Analysis; Animals; Antibodies; Antibodies, Neutralizing - immunology; Betacoronavirus - genetics; Betacoronavirus - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Clinical Trials, Phase III as Topic; Coronaviridae; Coronavirus Infections - genetics; Coronavirus Infections - immunology; Coronavirus Infections - prevention & control; Coronavirus Infections - virology; Coronaviruses; COVID-19; COVID-19 Vaccines; Disease control; Female; Humanities and Social Sciences; Immunopathology; Lung - immunology; Lung - virology; Lymphocytes; Lymphocytes T; Mice; Middle East respiratory syndrome; mRNA; mRNA vaccines; multidisciplinary; Mutation; Nose - immunology; Nose - virology; Pandemics; Pandemics - prevention & control; Pneumonia, Viral - immunology; Pneumonia, Viral - prevention & control; Pneumonia, Viral - virology; Proteins; Respiratory diseases; RNA, Messenger - genetics; RNA, Viral - genetics; SARS-CoV-2; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Spike protein; Th1 Cells - immunology; Toll-Like Receptor 4 - agonists; Toll-Like Receptor 4 - immunology; Vaccines; Viral diseases; Viral Vaccines - chemistry; Viral Vaccines - genetics; Viral Vaccines - immunology; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-020-2622-0

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. mRNA-1273, an mRNA vaccine that encodes a stabilized prefusion-state severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, elicits robust immune responses and protects mice against replication of SARS-CoV-2 in the upper and lower airways.