Abstract
Background
Although the emergency phase of the COVID-19 pandemic is over, attention has remained focused towards ongoing vaccination programs and the protection of high risk populations. The DS-5670 lipid nanoparticle-mRNA vaccine platform contains SARS-CoV-2 spike protein receptor-binding domain (RBD)-derived antigen(s). We conducted studies to provide supporting evidence for DS-5670 as a source of seasonal boosters using RBD antigens from variant strains and different valency compositions.
Methods
Randomized, active-comparator, non-inferiority studies evaluated monovalent DS-5670a (original strain RBD; Study 146 in 4518 adults ≥18 years) or bivalent DS-5670a/b (original and omicron BA.4-5 RBDs; Study 212 in 701 participants ≥12 years) as boosters. Primary efficacy endpoints were the GMFR in serum neutralization titers against SARS-CoV-2 (original strain) at 4 weeks (day 29) after study drug administration (Study 146), and the GMT and seroresponse rate of anti-SARS-CoV-2 (omicron BA.5 strain) serum neutralization titers on day 29 (Study 212).
Results
We show that both studies exceed non-inferiority margins. In Study 146, day 29 adjusted geometric mean fold-rise ratios for DS-5670a are 1.464 (97.5% confidence intervals 1.112, 1.927) vs BNT162b2 and 1.772 (1.335, 2.353) vs mRNA-1273. In Study 212, day 29 adjusted geometric mean titer ratio (DS-5670a/b vs bivalent BNT162b2) is 1.712 (95% confidence intervals, 1.509, 1.944); the between-group difference in seroresponse is 21.4% (13.8, 28.6). Both DS-5670 compositions are effective against symptomatic COVID-19, with broad neutralization activity across omicron sub-lineages. No serious adverse events are associated with DS-5670 in either study.
Conclusions
This platform can be utilized to produce new vaccines against future SARS-CoV-2 variants.
Plain Language Summary
Initial COVID-19 vaccines, like BNT162b2 and mRNA-1273, used messenger RNA (mRNA) technology and required two doses. However, protection from these vaccines fades over time, and new virus variants pose ongoing health threats. To address this, seasonal booster vaccines are being developed. Here, we develop two different versions of the DS-5670 vaccine and test their performance as boosters in Japan, and compared with existing COVID-19 vaccines. Both versions of DS5670 were able to produce good immune responses against various SARS-CoV-2 strains and were at least as effective as existing vaccines. Our findings indicate that DS-5670 could serve as an effective seasonal booster, with potential for future adaptation to emerging strains.
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Data availability
Source data, including the de-identified individual participant data on completed studies and applicable supporting clinical trial documents, will be made available upon request at https://vivli.org/, and details on data sharing criteria and the procedure for requesting access can be found at https://vivli.org/ourmember/daiichi-sankyo/. In brief, users should sign up to Vivli, navigate to the page for each study (for study 146 are available at https://doi.org/10.25934/PR00011565; for study 212 are available at https://doi.org/10.25934/PR00011566), and request study details. In accordance with the EFPIA/PhRMA’s data sharing principles, the request of data sharing will be determined by both the study sponsor and independent review board and provided only to qualified researchers. In addition, it is necessary under global privacy laws to protect the privacy of the clinical trial participants. Thus, these tools are designed to provide data only to those who request it.
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Acknowledgements
This study was conducted by Daiichi Sankyo Co., Ltd. (Tokyo, Japan). The work to develop and produce a vaccine against SARS-CoV-2 was funded and supported by the Ministry of Health, Labor and Welfare (MHLW) and Japan Agency for Medical Research and Development (AMED) under Grant Number JP21nf0101625, as part of the initiatives to combat COVID-19. The authors would especially like to thank all the participants who took part in the studies, the investigators, and the staff at the study sites for their support in conducting the study. The authors also thank all members of the clinical study team for valuable advice and support in the performance of this study. Finally, the authors also thank Sally-Anne Mitchell, PhD, of McCann Health CMC, for providing medical writing support, which was funded by Daiichi Sankyo Co., Ltd.
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All authors attest they meet the ICMJE criteria for authorship. S.H., M.S., K.I., K.F., Y.S., M.K., K.T., S.S., S.M., N.J., T.N., and F.T. were all involved in the study design and conduct, and in data analysis and interpretation. All authors had access to the full dataset, contributed to writing and reviewing the manuscript, and provided final approval of the manuscript for submission.
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The authors declare the following competing interests: S.H., M.S., K.I., K.F., Y.S., M.K., K.T., S.S., S.M., N.J., and F.T. are current employees of Daiichi Sankyo Co., Ltd.; S.H., M.S., Y.S., M.K., K.T., and S.S. hold stock in Daiichi Sankyo Co., Ltd. and N.J. holds patents and other interests with Daiichi Sankyo Co., Ltd. T.N. was a medical advisor at Daiichi Sankyo Co., Ltd. during the conduct of the studies, and has also received remuneration from Takeda Pharmaceutical and EIKEN CHEMICAL and research funding from GSK. The study sponsor (Daiichi Sankyo Co., Ltd.) was involved in the design of the studies, data analysis, and manuscript preparation; MHLW and AMED had no role in study design, data analysis, or preparation of the manuscript.
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Hamada, S., Suda, M., Ishida, K. et al. Effectiveness, immunogenicity and safety of monovalent DS-5670a and bivalent DS-5670a/b SARS-CoV-2 vaccines: results from two randomized, active-comparator, non-inferiority trials. Commun Med (2026). https://doi.org/10.1038/s43856-025-01215-9
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DOI: https://doi.org/10.1038/s43856-025-01215-9
