tetano
Editor, Senior Moderator
Vaccine
. 2022 Jun 6;S0264-410X(22)00718-6.
doi: 10.1016/j.vaccine.2022.05.081. Online ahead of print.
Immunogenicity and protective efficacy of SARS-CoV-2 recombinant S-protein vaccine S-268019-b in cynomolgus monkeys
Masayuki Hashimoto[SUP] 1 [/SUP], Noriyo Nagata[SUP] 2 [/SUP], Tomoyuki Homma[SUP] 3 [/SUP], Hiroki Maeda[SUP] 4 [/SUP], Keiji Dohi[SUP] 5 [/SUP], Naomi M Seki[SUP] 6 [/SUP], Ken Yoshihara[SUP] 7 [/SUP], Naoko Iwata-Yoshikawa[SUP] 8 [/SUP], Nozomi Shiwa-Sudo[SUP] 9 [/SUP], Yusuke Sakai[SUP] 10 [/SUP], Masayuki Shirakura[SUP] 11 [/SUP], Noriko Kishida[SUP] 12 [/SUP], Tomoko Arita[SUP] 13 [/SUP], Yasushi Suzuki[SUP] 14 [/SUP], Shinji Watanabe[SUP] 15 [/SUP], Hideki Asanuma[SUP] 16 [/SUP], Takuhiro Sonoyama[SUP] 17 [/SUP], Tadaki Suzuki[SUP] 18 [/SUP], Shinya Omoto[SUP] 19 [/SUP], Hideki Hasegawa[SUP] 20 [/SUP]
Affiliations
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 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.
Keywords: Coronavirus disease 2019; Cynomolgus monkeys; Recombinant protein vaccine; S-268019-b; Severe acute respiratory syndrome coronavirus 2.
. 2022 Jun 6;S0264-410X(22)00718-6.
doi: 10.1016/j.vaccine.2022.05.081. Online ahead of print.
Immunogenicity and protective efficacy of SARS-CoV-2 recombinant S-protein vaccine S-268019-b in cynomolgus monkeys
Masayuki Hashimoto[SUP] 1 [/SUP], Noriyo Nagata[SUP] 2 [/SUP], Tomoyuki Homma[SUP] 3 [/SUP], Hiroki Maeda[SUP] 4 [/SUP], Keiji Dohi[SUP] 5 [/SUP], Naomi M Seki[SUP] 6 [/SUP], Ken Yoshihara[SUP] 7 [/SUP], Naoko Iwata-Yoshikawa[SUP] 8 [/SUP], Nozomi Shiwa-Sudo[SUP] 9 [/SUP], Yusuke Sakai[SUP] 10 [/SUP], Masayuki Shirakura[SUP] 11 [/SUP], Noriko Kishida[SUP] 12 [/SUP], Tomoko Arita[SUP] 13 [/SUP], Yasushi Suzuki[SUP] 14 [/SUP], Shinji Watanabe[SUP] 15 [/SUP], Hideki Asanuma[SUP] 16 [/SUP], Takuhiro Sonoyama[SUP] 17 [/SUP], Tadaki Suzuki[SUP] 18 [/SUP], Shinya Omoto[SUP] 19 [/SUP], Hideki Hasegawa[SUP] 20 [/SUP]
Affiliations
- PMID: 35691872
- DOI: 10.1016/j.vaccine.2022.05.081
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 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.
Keywords: Coronavirus disease 2019; Cynomolgus monkeys; Recombinant protein vaccine; S-268019-b; Severe acute respiratory syndrome coronavirus 2.