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- Title
Domain-based mRNA vaccines encoding spike protein N-terminal and receptor binding domains confer protection against SARS-CoV-2.
- Authors
Stewart-Jones, Guillaume B. E.; Elbashir, Sayda M.; Wu, Kai; Lee, Diana; Renzi, Isabella; Ying, Baoling; Koch, Matthew; Sein, Caralyn E.; Choi, Angela; Whitener, Bradley; Garcia-Dominguez, Dario; Henry, Carole; Woods, Angela; Ma, LingZhi; Montes Berrueta, Daniela; Avena, Laura E.; Quinones, Julian; Falcone, Samantha; Hsiao, Chiaowen J.; Scheaffer, Suzanne M.
- 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). Editor's summary: The initial SARS-CoV-2 mRNA vaccines changed the course of the coronavirus disease 2019 (COVID-19) pandemic. Because these first-generation vaccines were successful, there is now the opportunity to improve upon them. To do this, Stewart-Jones et al. generated domain-based mRNA vaccines that expressed only the N-terminal domain (NTD) and receptor binding domain (RBD) of the SARS-CoV-2 spike protein rather than the full-length spike protein. This NTD-RBD–based mRNA vaccine generated similar or superior immune responses to the original full-length spike protein-encoding vaccine when given as a primary vaccine or as a booster, translating into similar degrees of protection against SARS-CoV-2 challenge in mice. Importantly, the domain-based vaccine was also more stable at refrigerated temperatures than the full-length vaccine, an important feature for global distribution. —Courtney Malo
- Subjects
SARS-CoV-2 Omicron variant; SARS-CoV-2 Delta variant; PROTEIN receptors; COVID-19; BOOSTER vaccines
- Publication
Science Translational Medicine, 2023, Vol 15, Issue 713, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.adf4100