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

Kizzmekia S. Corbett; Darin 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; Kapil Bahl; Dario Garcia-Dominguez; LingZhi Ma; Isabella Renzi; Wing-Pui Kong; Stephen D. Schmidt; Lingshu Wang; Yi Zhang; Laura J. Stevens; Emily Phung; Lauren A. Chang; Rebecca J. Loomis; Nedim Emil Altaras; Elisabeth Narayanan; Mihir Metkar; Vlad Presnyak; Catherine Liu; Mark K. Louder; Wei Shi; Kwanyee Leung; Eun Sung Yang; Ande West; Kendra L. Gully; Nianshuang Wang; Daniel Wrapp; Nicole A. Doria-Rose; Guillaume Stewart-Jones; Hamilton Bennett; 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:10.1101/2020.06.11.145920

Summary

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.

Competing Interest Statement

K.S.C., N.W., J.S.M., and B.S.G. are inventors on International Patent Application No. WO/2018/081318 entitled Prefusion Coronavirus Spike Proteins and Their Use. K.S.C., O.M.A., G.B.H., N.W., D.W., J.S.M, and B.S.G. are inventors on US Patent Application No. 62/972,886 entitled 2019-nCoV Vaccine. R.S.B. filed an invention report for the SARS-CoV-2 MA virus (UNC ref. #18752).