Safety, immunogenicity, persistence and dose evaluation of the CS-2034 mRNA COVID-19 vaccine: a phase II randomized controlled trial in healthy Chinese adults.

BACKGROUND: Our objective was to evaluate the safety and immunogenicity of the COVID-19 mRNA vaccine (CS-2034) in Chinese adults, and to determine the optimal dosage with a favorable safety and immunogenicity profile. METHODS: This study was a phase II clinical trial conducted across multiple centers, employing a randomized, double-blinded, dose-exploration, placebo-controlled design which was registered at ClinicalTrials.gov under the identifier NCT05373472 (registration date: May 13, 2022). RESULTS: A total of 150 participants were randomized into low-dose vaccine, high-dose vaccine, and placebo groups. The vaccine CS-2034 was well tolerated, with adverse reactions largely mild to moderate and comparable across dose groups. Both dose levels induced strong neutralizing antibody responses against the ancestral SARS-CoV-2 strain, with high seroconversion and evidence of antibody persistence over time. In contrast, neutralizing activity against the Omicron BA.1 variant was limited and declined further after the peak response. CONCLUSIONS: The 0.3 mL dose (low-dose vaccine) was selected for further development based on comparable immunogenicity and lower reactogenicity. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov under the identifier NCT05373472 (registration date: May 13, 2022).