Immunogenicity and protective efficacy of SARS-CoV-2 recombinant S-protein vaccine S-268019-b in cynomolgus monkeys

• Published in: Vaccine Vol. 40; no. 31; pp. 4231 - 4241
• Main Authors: Hashimoto, Masayuki, Nagata, Noriyo, Homma, Tomoyuki, Maeda, Hiroki, Dohi, Keiji, Seki, Naomi M., Yoshihara, Ken, Iwata-Yoshikawa, Naoko, Shiwa-Sudo, Nozomi, Sakai, Yusuke, Shirakura, Masayuki, Kishida, Noriko, Arita, Tomoko, Suzuki, Yasushi, Watanabe, Shinji, Asanuma, Hideki, Sonoyama, Takuhiro, Suzuki, Tadaki, Omoto, Shinya, Hasegawa, Hideki
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 29.07.2022; Elsevier Limited; The Authors. Published by Elsevier Ltd
• Subjects: adjuvants; Allergy and Immunology; Animals; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Antigens; Cell-mediated immunity; Chromatography; Clinical trials; Coronavirus disease 2019; Coronaviruses; COVID-19; COVID-19 - prevention & control; COVID-19 - therapy; COVID-19 Serotherapy; COVID-19 vaccines; Cynomolgus monkeys; Dosage; dose response; Enzymes; genomics; humans; Immune response (humoral); Immunization; Immunization, Passive; Immunogenicity; Immunogenicity, Vaccine; Laboratories; Lung diseases; Lymphocytes T; Macaca fascicularis; messenger RNA; Monkeys; Neutralizing; pandemic; Pandemics; Proteins; Pseudoviridae; Recombinant protein vaccine; S-268019-b; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus; Squalene; throat; Vaccine efficacy; Vaccines; Viral diseases; Viral Vaccines; Viruses; Weight loss; United States > US; Japan; Cynomolgus monkeys; Severe acute respiratory syndrome coronavirus 2; Coronavirus disease 2019; Recombinant protein vaccine; S-268019-b
• DOI: 10.1016/j.vaccine.2022.05.081
• ISSN: 0264-410X; 1873-2518

•A novel SARS-CoV-2 recombinant spike (S)-protein vaccine S-268019-b was developed.•S-268019-b induced antibodies against S-protein and its receptor binding domain.•Neutralizing antibody was induced against SARS-CoV-2 and pseudovirus variants.•S-268019-b demonstrated protective efficacy against SARS-CoV-2 challenge.•S-268019-b was safe for use in cynomolgus macaques. 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 vaccine 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 µg 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.