SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness
Author:
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.ORCID
Abstract
SummaryA 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
73 articles.
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