Abstract
To address the urgent need for effective immunization strategies against SARS-CoV-2 variants, particularly in older adults who are more vulnerable to severe disease, we evaluated the safety and immunogenicity of the bivalent COVID-19 mRNA vaccine RBMRNA-405 as a third-dose booster in adults aged 18 years and older previously vaccinated with two doses of inactivated vaccine. In a single-center, randomized, positive-controlled phase I study in China, 60 healthy participants were assigned (2:1) to receive either a heterologous booster (RBMRNA-405) or a homologous booster (CoronaVac). Primary endpoints assessed solicited local and systemic adverse events within 14 days post-vaccination, while secondary endpoints evaluated long-term safety and humoral immunogenicity via anti-Spike IgG ELISA and live-virus neutralization. Local pain at the injection site was the most common adverse event, primarily mild-to-moderate, with no serious vaccine-related adverse events reported. RBMRNA-405 induced 3.30-fold higher neutralizing antibodies against Omicron BA.1 and 17.66-fold higher anti-Spike IgG titers compared to CoronaVac on day 14 post-boost (P < 0.0001), with robust responses in older adults, where age-related immune decline necessitates tailored immunization strategies.
Trial registration: Clinical Trial Main ID: NCT05897190. Date of Registration: 28/05/2023.
Data availability
Anonymized individual participant data will be made available when the study is complete, on reasonable requests made to the corresponding author. Proposals will be reviewed and approved by the sponsor, investigator, and collaborators on the basis of scientific merit. After approval of a proposal, data can be shared through a secure online platform. The trial protocol and statistical analysis plan will also be made available upon reasonable request to the corresponding author.
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Acknowledgements
We thank all the participants who volunteered for this study. We also acknowledge the contributions of clinical staff and nurses who provided help with sampling in the clinical trial.
Funding
Argorna Pharmaceuticals Co., Ltd. This study was an investigator-initiated trial (IIT). The funder had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
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Contributions
X.Y. was the principal investigator and J.H. was the co-principal investigator. X.Y. and J.H. conceived the trial and contributed to the protocol and design of the study. X.Y. led the implementation of the study. Y.W. performed the statistical analysis and has verified the underlying data. Y.O. and C.Z. drafted the original manuscript. X.Y., J.H., and B.Z. reviewed and revised the original draft. All authors contributed to the article and approved the submitted version.
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Competing interests
This study was an investigator-initiated trial (IIT). The sponsor/funder had no role in study design, data collection, data analysis, data interpretation, or writing of the trial report. This trial was sponsored by Argorna Pharmaceuticals, which provided the study vaccine RBMRNA-405. RBMRNA-405 was co-developed by Argorna and RiboBio. YO and BZ are employees of Argorna. CZ is an employee of RiboBio. The other authors declare no competing interests.
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Yong, X., He, J., Zhang, C. et al. Heterologous RBMRNA-405 mRNA booster enhances humoral immunity post-inactivated COVID-19 vaccination: a randomized clinical trial in adults and older through 12 months. Sci Rep (2026). https://doi.org/10.1038/s41598-026-45429-w
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DOI: https://doi.org/10.1038/s41598-026-45429-w
