Phase 1 Trial of mRNA-CR-04 Vaccine Targeting SARS-CoV-2 Omicron BA.5 in Adults 18-49

Overview

This Phase 1 randomized controlled trial evaluated the safety and immunogenicity of the novel mRNA-CR-04 vaccine encoding the SARS-CoV-2 BA.5 spike protein in adults aged 18 to 49. The vaccine was generally well tolerated across doses from 3 to 100 µg and elicited robust neutralizing antibody responses against BA.5 and cross-neutralization against the wild-type virus, with titers waning but remaining above baseline at 6 months.

Background

mRNA vaccines have been pivotal in controlling the COVID-19 pandemic due to their rapid development and strong immune responses. These vaccines deliver synthetic mRNA encoding viral antigens within lipid nanoparticles, inducing both humoral and cellular immunity without risk of genomic integration. The mRNA-CR-04 vaccine is a novel construct targeting the SARS-CoV-2 Omicron BA.5 variant spike protein, developed to address emerging variants and improve booster immunogenicity. This first-in-human Phase 1 study assessed safety and immune responses following a single booster dose in previously vaccinated healthy adults.

Data Highlights

Key Findings

• The mRNA-CR-04 vaccine was generally well tolerated with mostly mild to moderate and transient adverse events.
• Grade 3 reactogenicity occurred only in the highest dose group (100 µg) at a rate of 16.7%.
• All vaccine doses elicited notable neutralizing antibody titers against the BA.5 variant and cross-neutralization against the wild-type SARS-CoV-2 (D614G).
• Immune response magnitude increased with higher vaccine doses.
• Neutralizing antibody titers waned by 6 months post-vaccination but remained above baseline levels.
• No safety concerns causally related to the vaccine were identified based on clinical and laboratory data.

Clinical Implications

The mRNA-CR-04 vaccine demonstrates a favorable safety profile and induces robust neutralizing antibody responses against the Omicron BA.5 variant, supporting its potential as a booster vaccine. Dose-dependent immunogenicity suggests flexibility in dosing strategies to balance reactogenicity and immune response. These findings warrant further clinical development of this mRNA platform for variant-specific COVID-19 vaccines.

Conclusion

This first-in-human Phase 1 study confirms that the mRNA-CR-04 vaccine targeting SARS-CoV-2 BA.5 is safe and immunogenic in adults aged 18 to 49, with durable neutralizing antibody responses up to 6 months. Further investigation in larger trials is justified to optimize dosing and confirm efficacy.

References

1. NCT05972993 Clinical Trial Report 2025 -- Phase 1 Study of mRNA-CR-04 Vaccine