Development of SARS-CoV-2 mRNA vaccines encoding spike N-terminal and receptor binding domains

Stewart-Jones, G.; Elbashir, S. M.; Wu, K.; Lee, D.; Renzi, I.; Ying, B.; Koch, M.; Sein, C. E.; Choi, A.; Whitener, B.; Garcia-Dominguez, D.; Henry, C.; Woods, A.; Ma, L.; Montes Berrueta, D.; Avena, L. E.; Quinones, J.; Falcone, S.; Hsiao, C. J.; Scheaffer, S. M.; Thackray, L. B.; White, P.; Diamond, M. S.; Edwards, D. K.; Carfi, A.

doi:10.1101/2022.10.07.511319

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bioRxiv · 10.1101/2022.10.07.511319

Development of SARS-CoV-2 mRNA vaccines encoding spike N-terminal and receptor binding domains

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Abstract

With the success of mRNA vaccines against coronavirus disease 2019 (COVID-19), strategies can now focus on improving vaccine potency, breadth, and stability. We present the design and preclinical evaluation of domain-based mRNA vaccines encoding the wild-type spike-protein receptor-binding (RBD) and/or N-terminal domains (NTD). An NTD-RBD linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2-8{degrees}C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses and protection from viral challenge were observed against wild-type, beta, delta, or omicron (BA. 1) compared with mRNA-1273 immunized mice, especially at lower vaccine dosages. These results support clinical assessment of mRNA-1283 (NCT05137236). One Sentence SummaryA domain-based mRNA vaccine, mRNA-1283, is immunogenic and protective against SARS-CoV-2 and emerging variants in mice.

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Stewart-Jones, G., Elbashir, S. M., Wu, K., Lee, D., Renzi, I., Ying, B., Koch, M., Sein, C. E., Choi, A., Whitener, B., Garcia-Dominguez, D., Henry, C., Woods, A., Ma, L., Montes Berrueta, D., Avena, L. E., Quinones, J., Falcone, S., Hsiao, C. J., Scheaffer, S. M., Thackray, L. B., White, P., Diamond, M. S., Edwards, D. K., Carfi, A.. 2022-10-07. Development of SARS-CoV-2 mRNA vaccines encoding spike N-terminal and receptor binding domains. https://doi.org/10.1101/2022.10.07.511319

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