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

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

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.