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Results from a preclinical study in rodents and a Phase 1/2, randomized, double-blind, placebo-controlled, parallel-group study of COVID-19 vaccine S-268019-a in Japanese adults.
Sonoyama, Takuhiro; Iwata, Satoshi; Shinkai, Masaharu; Iwata-Yoshikawa, Naoko; Shiwa-Sudo, Nozomi; Hemmi, Takuya; Ainai, Akira; Nagata, Noriyo; Matsunaga, Nobuaki; Tada, Yukio; Homma, Tomoyuki; Omoto, Shinya; Yokokawa Shibata, Risa; Igarashi, Kenji; Suzuki, Tadaki; Hasegawa, Hideki; Ariyasu, Mari.
  • Sonoyama T; Shionogi & Co., Ltd., Drug Development and Regulatory Science Division, 8F, Nissay Yodoyabashi East Bldg., 3-3-13, Imabashi, Chuo-ku, Osaka 541-0042, Japan.
  • Iwata S; National Cancer Center Hospital, Department of Infectious Diseases, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
  • Shinkai M; Department of Respiratory Medicine, Tokyo Shinagawa Hospital, 6-3-22, Higashioi, Shinagawa-ku, Tokyo 140-8522, Japan.
  • Iwata-Yoshikawa N; Department of Pathology, National Institute of Infectious Diseases, 4-7-1, Gakuen Musashimurayama-shi, Tokyo 208-0011, Japan.
  • Shiwa-Sudo N; Department of Pathology, National Institute of Infectious Diseases, 4-7-1, Gakuen Musashimurayama-shi, Tokyo 208-0011, Japan.
  • Hemmi T; Department of Pathology, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
  • Ainai A; Department of Pathology, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
  • Nagata N; Department of Pathology, National Institute of Infectious Diseases, 4-7-1, Gakuen Musashimurayama-shi, Tokyo 208-0011, Japan.
  • Matsunaga N; AMR Clinical Reference Center, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
  • Tada Y; Shionogi & Co., Ltd., Drug Development and Regulatory Science Division, 8F, Nissay Yodoyabashi East Bldg., 3-3-13, Imabashi, Chuo-ku, Osaka 541-0042, Japan.
  • Homma T; Shionogi & Co., Ltd., Pharmaceutical Research Division, 1-1, Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan.
  • Omoto S; Shionogi & Co., Ltd., Pharmaceutical Research Division, 1-1, Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan.
  • Yokokawa Shibata R; Shionogi & Co., Ltd., Drug Development and Regulatory Science Division, 8F, Nissay Yodoyabashi East Bldg., 3-3-13, Imabashi, Chuo-ku, Osaka 541-0042, Japan.
  • Igarashi K; Shionogi & Co., Ltd., Drug Development and Regulatory Science Division, 8F, Nissay Yodoyabashi East Bldg., 3-3-13, Imabashi, Chuo-ku, Osaka 541-0042, Japan.
  • Suzuki T; Department of Pathology, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
  • Hasegawa H; Research Center for Influenza and Respiratory Virus, National Institute of Infectious Diseases, 4-7-1, Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.
  • Ariyasu M; Shionogi & Co., Ltd., Drug Development and Regulatory Science Division, 8F, Nissay Yodoyabashi East Bldg., 3-3-13, Imabashi, Chuo-ku, Osaka 541-0042, Japan. Electronic address: mari.tatsuno@shionogi.co.jp.
Vaccine ; 41(11): 1834-1847, 2023 03 10.
Article in English | MEDLINE | ID: covidwho-2282146
ABSTRACT

BACKGROUND:

In early 2020, developing vaccines was an urgent need for preventing COVID-19 from a contingency perspective.

METHODS:

S-268019-a is a recombinant protein-based vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprising a modified recombinant spike protein antigen adjuvanted with agatolimod sodium, a Toll-like receptor-9 agonist. In the preclinical phase, it was administered intramuscularly twice at a 2-week interval in 7-week-old mice. Immunogenicity was assessed, and the mice were challenged intranasally with mouse-adapted SARS-CoV-2 at 2 and 8 weeks, respectively, after the second immunization. After confirming the preclinical effect, a Phase 1/2, randomized, parallel-group clinical study was conducted in healthy adults (aged 20-64 years). All participants received 2 intramuscular injections at various combinations of the antigen and the adjuvant (S-910823/agatolimod sodium, in µg 12.5/250, 25/250, 50/250, 25/500, 50/500, 100/500, 10/500, 100/100, 200/1000) or placebo (saline) in an equivalent volume at a 3-week interval and were followed up until Day 50 in this interim analysis.

RESULTS:

In the preclinical studies, S-268019-a was safe and elicited robust immunoglobulin G (IgG) and neutralizing antibody responses in mice. When challenged with SARS-CoV-2, all S-268019-a-treated mice survived and maintained weight until 10 days, whereas all placebo- or adjuvant-treated (without antigen) mice died within 6 days. In the Phase 1/2 trial, although S-268019-a was well tolerated in adult participants, was safe up to Day 50, and elicited robust anti-spike protein IgG antibodies, it did not elicit sufficient neutralizing antibody levels.

CONCLUSIONS:

The S-268019-a vaccine was not sufficiently immunogenic in Japanese adults despite robust immunogenicity and efficacy in mice. Our results exemplify the innate challenges in translating preclinical data in animals to clinical trials, and highlight the need for continued research to overcome such barriers. (jRCT2051200092).
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunogenicity, Vaccine / COVID-19 Vaccines / COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Vaccines Limits: Animals / Humans Language: English Journal: Vaccine Year: 2023 Document Type: Article Affiliation country: J.vaccine.2022.12.025

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunogenicity, Vaccine / COVID-19 Vaccines / COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Vaccines Limits: Animals / Humans Language: English Journal: Vaccine Year: 2023 Document Type: Article Affiliation country: J.vaccine.2022.12.025