Longitudinal analysis of immune responses to SARS-CoV-2 recombinant vaccine S-268019-b in phase 1/2 prime-boost study

Masaya Fujitani ¹ Xiuyuan Lu ² Ryo Shinnakasu ³ Takeshi Inoue ³ Yujiro Kidani ¹ Naomi M Seki ¹ Satoru Ishida ¹ Shungo Mitsuki ¹ Takeshi Ishihara ¹ Miwa Aoki ¹ Akio Suzuki ¹ Koji Takahashi ¹ Masahiro Takayama ⁴ Takeshi Ota ⁴ Satoshi Iwata ⁵ Risa Yokokawa Shibata ⁶ Takuhiro Sonoyama ⁶ Mari Ariyasu ⁶ Ayumi Kitano ⁷ Tommy Terooatea ⁷ Jordan Kelly Villa ⁷ Kazuo YAMASHITA ⁷ Sho Yamasaki ^10,8,9 Tomohiro Kurosaki ^3,9 Shinya Omoto ^1*

• ¹ Vaccine Business Division, Shionogi & Co., Ltd., Osaka, Japan
• ² Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Osaka, Japan
• ³ Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
• ⁴ Pharmaceutical Technology Research Division, Shionogi & Co., Ltd., Osaka, Japan
• ⁵ Department of Microbiology, Tokyo Medical University, Tokyo, Japan
• ⁶ Drug Development and Regulatory Science Division, Shionogi & Co., Ltd., Osaka, Japan
• ⁷ KOTAI Biotechnologies, Inc., Osaka, Japan
• ⁸ Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
• ⁹ Center for Infectious Disease Education and Research (CiDER), Osaka University, Suita, Osaka, Japan
• ¹⁰ Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University,, Osaka, Japan

Background: The durability of vaccine-induced immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for preventing infection, especially severe disease.Methods: This 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. Results: Booster 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 Tcell 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. Conclusion: These 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).