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Longitudinal analysis of B- and T-cell responses to SARS-CoV-2 recombinant S-protein vaccine S-268019-b in phase 1/2 priming and booster study

Fujitani, M.; Lu, X.; Shinnakasu, R.; Inoue, T.; Kidani, Y.; Seki, N. M.; Ishida, S.; Mitsuki, S.; Ishihara, T.; Aoki, M.; Suzuki, A.; Takahashi, K.; Takayama, M.; Ota, T.; Iwata, S.; Yokokawa Shibata, R.; Sonoyama, T.; Ariyasu, M.; Kitano, A.; Terooatea, T.; Kelly Villa, J.; Yamashita, K.; Yamasaki, S.; Kurosaki, T.; Omoto, S.

2024-10-03 infectious diseases
10.1101/2024.10.01.24314659 medRxiv
Show abstract

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. 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. 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 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. 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).

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