Safety and Immunogenicity of mRNA-1283 COVID-19 Vaccine Targeting Spike Protein Domains

Overview

The phase 2a study demonstrated that the investigational mRNA-1283 vaccine, encoding SARS-CoV-2 spike protein receptor-binding and N-terminal domains, was well tolerated and elicited higher neutralizing antibody responses compared to the original mRNA-1273 vaccine. The bivalent and Omicron BA.1 formulations also increased neutralizing antibodies against respective variants, with antibody responses persisting for up to one year.

Background

mRNA-based vaccines such as mRNA-1273 have been effective in preventing COVID-19 and severe outcomes. However, challenges including ultralow temperature storage limit their global deployment. The mRNA-1283 vaccine encodes only the immunodominant receptor-binding and N-terminal domains of the spike protein, resulting in a smaller mRNA molecule with potentially improved stability and immunogenicity. This study evaluated the safety and immune response of mRNA-1283 and its variant formulations as booster doses in adults previously vaccinated with mRNA-1273.

Data Highlights

Key Findings

• mRNA-1283 vaccine encoding RBD and NTD domains elicited higher neutralizing antibody responses than mRNA-1273 at day 29 post-vaccination.
• All tested doses of mRNA-1283 and its variant formulations were well tolerated with no new safety concerns.
• Bivalent mRNA-1283.211 induced robust neutralizing antibodies against both original SARS-CoV-2 and Beta variant.
• Monovalent mRNA-1283.529 targeting Omicron BA.1 significantly increased neutralizing antibodies against this variant.
• Neutralizing antibody responses remained detectable up to one year after vaccination.
• Shorter mRNA sequence in mRNA-1283 may improve vaccine stability and facilitate global distribution.

Clinical Implications

The improved immunogenicity and favorable safety profile of mRNA-1283 suggest it may serve as an effective booster vaccine with potential advantages in storage and distribution. Its variant-specific formulations provide flexibility to address emerging SARS-CoV-2 variants, supporting its use in ongoing vaccination strategies. Clinicians should consider these findings when selecting booster options for previously vaccinated individuals.

Conclusion

mRNA-1283 and its variant formulations are safe and elicit strong, durable neutralizing antibody responses, outperforming the original mRNA-1273 vaccine. These results support further development and potential clinical use of mRNA-1283 as a next-generation COVID-19 vaccine.

References

1. Moderna Clinical Trial NCT05137236 -- Evaluation of Safety and Immune Response to mRNA Vaccine Targeting SARS-CoV-2 Spike Protein Domains