- Masayuki Hashimoto, N. Nagata, T. Homma, Hiroki Maeda, K. Dohi, Naomi M. Seki, Ken Yoshihara, N. Iwata-Yoshikawa, N. Shiwa-Sudo, Y. Sakai, Masayuki Shirakura, N. Kishida, Tomoko Arita, Yasushi Suzuki, Shinji Watanabe, H. Asanuma, T. Sonoyama, Tadaki Suzuki, S. Omoto, H. Hasegawa. 2022. Immunogenicity and protective efﬁcacy of SARS-CoV-2 recombinant S-protein vaccine S-268019-b in cynomolgus monkeys. Abstract: The vaccine S-268019-b is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)- protein vaccine consisting of full-length recombinant SARS-CoV-2 S-protein (S-910823) as antigen, mixed with the squalene-based adjuvant A-910823. The current study evaluated the immunogenicity of S- 268019-b using various doses of S-910823 and its vaccine efﬁcacy against SARS-CoV-2 challenge in cynomolgus monkeys. The different doses of S-910823 combined with A-910823 were intramuscularly administered twice at a 3-week interval. Two weeks after the second dosing, dose-dependent humoral immune responses were observed with neutralizing antibody titers being comparable to that of human convalescent plasma. Pseudoviruses harboring S proteins from Beta and Gamma SARS-CoV-2 variants displayed approximately 3- to 4-fold reduced sensitivity to neutralizing antibodies induced after two vac- cine doses compared with that against ancestral viruses, whereas neutralizing antibody titers were reduced >14-fold against the Omicron variant. Cellular immunity was also induced with a relative Th1 polarized response. No adverse clinical signs or weight loss associated with the vaccine were observed, suggesting safety of the vaccine in cynomolgus monkeys. Immunization with 10 l g of S-910823 with A-910823 demonstrated protective efﬁcacy against SARS-CoV-2 challenge according to genomic and subgenomic viral RNA transcript levels in nasopharyngeal, throat, and rectal swab specimens. Pathological analysis revealed no detectable vaccine-dependent enhancement of disease in the lungs of challenged vaccinated monkeys. The current ﬁndings provide fundamental information regarding vaccine doses for human trials and support the development of S-268019-b as a safe and effective vaccine for controlling the current pandemic, as well as general protection against SARS-CoV-2 moving forward.
