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Preclinical study of a DNA vaccine targeting SARS-CoV-2.
Hayashi, Hiroki; Sun, Jiao; Yanagida, Yuka; Otera, Takako; Kubota-Koketsu, Ritsuko; Shioda, Tatsuo; Ono, Chikako; Matsuura, Yoshiharu; Arase, Hisashi; Yoshida, Shota; Nakamaru, Ryo; Ju, Nan; Ide, Ryoko; Tenma, Akiko; Kawabata, Sotaro; Ehara, Takako; Sakaguchi, Makoto; Tomioka, Hideki; Shimamura, Munehisa; Okamoto, Sachiko; Amaishi, Yasunori; Chono, Hideto; Mineno, Junichi; Komatsuno, Takao; Saito, Yoshimi; Rakugi, Hiromi; Morishita, Ryuichi; Nakagami, Hironori.
  • Hayashi H; Department of Health Development and Medicine, Osaka University Graduate School of Medicine, Japan.
  • Sun J; Department of Health Development and Medicine, Osaka University Graduate School of Medicine, Japan.
  • Yanagida Y; Department of Health Development and Medicine, Osaka University Graduate School of Medicine, Japan.
  • Otera T; Department of Health Development and Medicine, Osaka University Graduate School of Medicine, Japan; Anges Inc, Japan.
  • Kubota-Koketsu R; Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Japan; Laboratory of Virus Control, Center for Infectious Disease Education and Research, Osaka University, Suita, Japan.
  • Shioda T; Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Japan.
  • Ono C; Laboratory of Virus Control, Center for Infectious Disease Education and Research, Osaka University, Suita, Japan; Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Matsuura Y; Laboratory of Virus Control, Center for Infectious Disease Education and Research, Osaka University, Suita, Japan; Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Arase H; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Japan; Laboratory of Immunochemistry, WPI Immunology Frontier Research Centre, Osaka University, Japan.
  • Yoshida S; Department of Health Development and Medicine, Osaka University Graduate School of Medicine, Japan; Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Japan.
  • Nakamaru R; Department of Health Development and Medicine, Osaka University Graduate School of Medicine, Japan; Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Japan.
  • Ju N; Department of Health Development and Medicine, Osaka University Graduate School of Medicine, Japan; Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Japan.
  • Ide R; FunPep Co., Ltd, Japan.
  • Tenma A; FunPep Co., Ltd, Japan.
  • Kawabata S; FunPep Co., Ltd, Japan.
  • Ehara T; FunPep Co., Ltd, Japan.
  • Sakaguchi M; FunPep Co., Ltd, Japan.
  • Tomioka H; FunPep Co., Ltd, Japan.
  • Shimamura M; Department of Health Development and Medicine, Osaka University Graduate School of Medicine, Japan.
  • Okamoto S; Takara Bio Inc., Shiga, Japan.
  • Amaishi Y; Takara Bio Inc., Shiga, Japan.
  • Chono H; Takara Bio Inc., Shiga, Japan.
  • Mineno J; Takara Bio Inc., Shiga, Japan.
  • Komatsuno T; Anges Inc, Japan.
  • Saito Y; Anges Inc, Japan.
  • Rakugi H; Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Japan.
  • Morishita R; Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Japan.
  • Nakagami H; Department of Health Development and Medicine, Osaka University Graduate School of Medicine, Japan; Lead contact, Japan. Electronic address: nakagami@gts.med.osaka-u.ac.jp.
Curr Res Transl Med ; 70(4): 103348, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1796171
ABSTRACT
To fight against the worldwide COVID-19 pandemic, the development of an effective and safe vaccine against SARS-CoV-2 is required. As potential pandemic vaccines, DNA/RNA vaccines, viral vector vaccines and protein-based vaccines have been rapidly developed to prevent pandemic spread worldwide. In this study, we designed plasmid DNA vaccine targeting the SARS-CoV-2 Spike glycoprotein (S protein) as pandemic vaccine, and the humoral, cellular, and functional immune responses were characterized to support proceeding to initial human clinical trials. After intramuscular injection of DNA vaccine encoding S protein with alum adjuvant (three times at 2-week intervals), the humoral immunoreaction, as assessed by anti-S protein or anti-receptor-binding domain (RBD) antibody titers, and the cellular immunoreaction, as assessed by antigen-induced IFNγ expression, were up-regulated. In IgG subclass analysis, IgG2b was induced as the main subclass. Based on these analyses, DNA vaccine with alum adjuvant preferentially induced Th1-type T cell polarization. We confirmed the neutralizing action of DNA vaccine-induced antibodies by a binding assay of RBD recombinant protein with angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, and neutralization assays using pseudo-virus, and live SARS-CoV-2. Further B cell epitope mapping analysis using a peptide array showed that most vaccine-induced antibodies recognized the S2 and RBD subunits. Finally, DNA vaccine protected hamsters from SARS-CoV-2 infection. In conclusion, DNA vaccine targeting the spike glycoprotein of SARS-CoV-2 might be an effective and safe approach to combat the COVID-19 pandemic.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Vaccines / Vaccines, DNA / COVID-19 Type of study: Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: Curr Res Transl Med Year: 2022 Document Type: Article Affiliation country: J.retram.2022.103348

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Vaccines / Vaccines, DNA / COVID-19 Type of study: Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: Curr Res Transl Med Year: 2022 Document Type: Article Affiliation country: J.retram.2022.103348