AUTHOR=Fujitani Masaya , Lu Xiuyuan , Shinnakasu Ryo , Inoue Takeshi , Kidani Yujiro , Seki Naomi M. , Ishida Satoru , Mitsuki Shungo , Ishihara Takeshi , Aoki Miwa , Suzuki Akio , Takahashi Koji , Takayama Masahiro , Ota Takeshi , Iwata Satoshi , Shibata Risa Yokokawa , Sonoyama Takuhiro , Ariyasu Mari , Kitano Ayumi , Terooatea Tommy , Kelly Villa Jordan , Yamashita Kazuo , Yamasaki Sho , Kurosaki Tomohiro , Omoto Shinya TITLE=Longitudinal analysis of immune responses to SARS-CoV-2 recombinant vaccine S-268019-b in phase 1/2 prime-boost study JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1550279 DOI=10.3389/fimmu.2025.1550279 ISSN=1664-3224 ABSTRACT=BackgroundThe durability of vaccine-induced immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for preventing infection, especially severe disease.MethodsThis follow-up report from a phase 1/2 study of S-268019-b (a recombinant spike protein vaccine) after homologous booster vaccination confirms its long-term safety, tolerability, and immunogenicity.ResultsBooster vaccination with S-268019-b resulted in an enhancement of serum neutralizing antibody (NAb) titers and a broad range of viral neutralization. Single-cell immune profiling revealed persistent and mature antigen-specific memory B cells and T follicular helper cells, with increased B-cell receptor diversity. The expansion of B- and T-cell repertoires and presence of cross-reactive NAbs targeting conserved epitopes within the receptor-binding domain following a booster accounted for the broad-spectrum neutralizing activity.ConclusionThese findings highlight the potential of S-268019-b to provide broad and robust protection against a range of SARS-CoV-2 variants, addressing a critical challenge in the ongoing fight against coronavirus disease 2019 (COVID-19).