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

OPEN bioRxiv : the preprint server for biology | 25 Jun 2020

KS Corbett, D Edwards, SR Leist, OM Abiona, S Boyoglu-Barnum, RA Gillespie, S Himansu, A Schäfer, CT Ziwawo, AT DiPiazza, KH Dinnon, SM Elbashir, CA Shaw, A Woods, EJ Fritch, DR Martinez, KW Bock, M Minai, BM Nagata, GB Hutchinson, K Bahl, D Garcia-Dominguez, L Ma, I Renzi, WP Kong, SD Schmidt, L Wang, Y Zhang, LJ Stevens, E Phung, LA Chang, RJ Loomis, NE Altaras, E Narayanan, M Metkar, V Presnyak, C Liu, MK Louder, W Shi, K Leung, ES Yang, A West, KL Gully, N Wang, D Wrapp, NA Doria-Rose, G Stewart-Jones, H Bennett, MC Nason, TJ Ruckwardt, JS McLellan, MR Denison, JD Chappell, IN Moore, KM Morabito, JR Mascola, RS Baric, A Carfi and BS Graham
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.
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