Immunogenicity and safety of DS-5670d, an mRNA-based COVID-19 vaccine targeting omicron XBB.1.5: Results from a phase 3, randomized, active-controlled study in adults and children aged ≥12 years
Authors: Kawamoto Ami , Hashida Masahiro , Ishida Katsuyasu , Furihata Kei , Ota Aisaku , Takahashi Kaori , Sakakibara Sachiko , Nakano Takashi , Takeshita Fumihiko 
Published: November 2024

AbstractBackgroundMany people worldwide have now acquired immune responses against the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) following previous vaccination and/or infection. As a result, national vaccination programs are now implementing a simplified schedule of single-dose administration and seasonal boosters. In this phase 3 non-inferiority study, we assessed the immunogenicity and safety of a single dose of the lipid nanoparticle-messenger ribonucleic acid vaccine DS-5670d, a monovalent composition for the 2023/24 season, containing an omicron XBB.1.5-derived antigen.Methods and FindingsAdults and children aged ≥12 years were stratified according to their history of both prior SARS-CoV-2 infection plus prior coronavirus disease 2019 (COVID-19) vaccination (subpopulation A), prior infection only (subpopulation B), prior vaccination only (subpopulation C), or no history of either infection or vaccination (subpopulation D), and randomly assigned (1:1) to receive DS-5670d or monovalent BNT162b2 omicron XBB.1.5. In the combined ABC subpopulations (DS-5670d,n= 362 vs BNT162b2,n= 363), the adjusted geometric mean titer ratio of blood neutralizing activity against SARS-CoV-2 (omicron XBB.1.5) was 1.218 (95% confidence interval [CI], 1.059, 1.401) and the seroresponse rates were 87.3% (DS-5670d) and 82.9% (BNT162b2) with an adjusted difference of 4.5% (95% CI, –0.70, 9.71). Both results exceeded prespecified non-inferiority margins and the study met the primary endpoint. Immunogenicity data in the overall ABCD population also met non-inferiority criteria. There were no apparent differences in immunogenicity according to age or sex, and analyses suggested that even unvaccinated persons achieved an adequate immune response following a single dose of DS-5670d. There were no major differences in the incidence or severity of adverse events between the study vaccination groups.ConclusionsA single dose of DS-5670d was immunogenically non-inferior to BNT162b2 and acceptably safe in persons with or without a history of prior infection and/or vaccination.Trial RegistrationJapan Registry of Clinical Trials (jRCT2031230424)Author summaryWhy was this study done?The global emergency response against the coronavirus disease 2019 (COVID-19) pandemic is now being superseded by annual immunization using an updated vaccine composition to reduce the disease burden associated with newly emerging variants.We conducted a comparative study of two newly authorized updated vaccine compositions containing the antigen derived from omicron XBB.1.5, which was recommended for the 2023/24 season.We intended to assess the immunogenicity and safety of a single dose of DS-5670d compared with BNT162b2 in Japanese adults and children aged ≥12 years.What did the researchers do and find?In persons who had received prior vaccination, or who had previously had COVID-19, or both, DS-5670d was non-inferior to BNT162b2 in terms of blood neutralizing activity and seroresponse rates, and immune responses were not influenced by age or sex.Among unvaccinated persons, those who had been exposed to SARS-CoV-2 by prior infection achieved an adequate immune response following a single dose of DS-5670d; however, the group who had had no previous exposure at all was too small to properly evaluate.There were no major differences in the frequency or severity of adverse events between the study vaccination groups, and there were no DS-5670d-related serious adverse events.What do these findings mean?DS-5670d was immunogenically non-inferior to BNT162b2, which has already been widely administered in Japan.There were no new critical safety concerns associated with DS-5670d, suggesting that it could be a useful SARS-CoV-2 vaccine option.Taken together, the results from this study of DS-5670d and those from previous studies evaluating other compositions of DS-5670, i.e., those containing antigens from different strains of SARS-CoV-2, provide corroborating evidence that the DS-5670 vaccine platform can be applied to produce effective and safe seasonal vaccines against future emerging strains.