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

Corbett, K. S.; Edwards, D.; Leist, S. R.; Abiona, O. M.; Boyoglu-Barnum, S.; Gillespie, R. A.; Himansu, S.; Schafer, A.; Ziwawo, C. T.; DiPiazza, A. T.; Dinnon, K. H.; Elbashir, S. M.; Shaw, C. A.; Woods, A.; Fritch, E. J.; Martinez, D. R.; Bock, K. W.; Minai, M.; Nagata, B. M.; Hutchinson, G. B.; Bahl, K.; Garcia-Dominguez, D.; Ma, L.; Renzi, I.; Kong, W.-P.; Schmidt, S. D.; Wang, L.; Zhang, Y.; Stevens, L. J.; Phung, E.; Chang, L. A.; Loomis, R. J.; Altaras, N. E.; Narayanan, E.; Metkar, M.; Presnyak, V.; Liu, C.; Louder, M. K.; Shi, W.; Leung, K.; Yang, E. S.; West, A.; Gully, K. L.; Wang,

doi:10.1101/2020.06.11.145920

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bioRxiv · 10.1101/2020.06.11.145920

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

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Abstract

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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Corbett, K. S., Edwards, D., Leist, S. R., Abiona, O. M., Boyoglu-Barnum, S., Gillespie, R. A., Himansu, S., Schafer, A., Ziwawo, C. T., DiPiazza, A. T., Dinnon, K. H., Elbashir, S. M., Shaw, C. A., Woods, A., Fritch, E. J., Martinez, D. R., Bock, K. W., Minai, M., Nagata, B. M., Hutchinson, G. B., Bahl, K., Garcia-Dominguez, D., Ma, L., Renzi, I., Kong, W.-P., Schmidt, S. D., Wang, L., Zhang, Y., Stevens, L. J., Phung, E., Chang, L. A., Loomis, R. J., Altaras, N. E., Narayanan, E., Metkar, M., Presnyak, V., Liu, C., Louder, M. K., Shi, W., Leung, K., Yang, E. S., West, A., Gully, K. L., Wang,. 2020-06-11. SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness. https://doi.org/10.1101/2020.06.11.145920

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