Domain-based mRNA vaccines encoding spike protein N-terminal and receptor binding domains confer protection against SARS-CoV-2

Guillaume B.E. Stewart-Jones, Sayda M. Elbashir, Kai Wu, Diana Lee, Isabella Renzi, Baoling Ying, Matthew Koch, Caralyn E. Sein, Angela Choi, Bradley Whitener, Dario Garcia-Dominguez, Carole Henry, Angela Woods, Ling Zhi Ma, Daniela Montes Berrueta, Laura E. Avena, Julian Quinones, Samantha Falcone, Chiaowen J. Hsiao, Suzanne M. ScheafferLarissa B. Thackray, Phil White, Michael S. Diamond, Darin K. Edwards, Andrea Carfi

Research output: Contribution to journalArticlepeer-review

Abstract

With the success of messenger RNA (mRNA) vaccines against coronavirus disease 2019, strategies can now focus on improving vaccine potency, breadth, and stability. We designed and evaluated domain-based mRNA vaccines encoding the wild-type spike protein receptor binding domain (RBD) or N-terminal domain (NTD) alone or in combination. An NTD-RBD-linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2° to 8°C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In BALB/c mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses from viral challenge were observed against wild-type, beta, delta, or omicron (BA.1) viruses compared with mRNA-1273-immunized mice, especially at lower vaccine dosages. K18-hACE2 mice immunized with mRNA-1283 or mRNA-1273 as a primary series demonstrated similar degrees of protection from challenge with SARS-CoV-2 Delta and Omicron variants at all vaccine dosages. These results support clinical assessment of mRNA-1283, which has now entered clinical trials (NCT05137236).

Original languageEnglish
Article numbereadf4100
JournalScience translational medicine
Volume15
Issue number713
DOIs
StatePublished - Sep 2023

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