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Investigation of the mechanism of inducing the original antigenic sin phenomenon associated with influenza virus infection

Research Project

Project/Area Number 18K07135
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49060:Virology-related
Research InstitutionHokkaido University

Principal Investigator

SHINGAI Masashi  北海道大学, 人獣共通感染症国際共同研究所, 准教授 (80421981)

Co-Investigator(Kenkyū-buntansha) 喜田 宏  北海道大学, 人獣共通感染症リサーチセンター, 特別招へい教授 (10109506)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsインフルエンザ / ウイルス / ワクチン / 免疫 / 抗原原罪 / インフルエンザウイルス / レパトア解析
Outline of Final Research Achievements

Using a mouse model of influenza virus infection, we confirmed that the original antigenic sin does indeed occur. Repertoire analysis of immunoglobulins showed that the PR8-infected group had a higher diversity of repertoires than the non-infected group. This suggests that the infection induced a greater diversity of immunoglobulins. They also analyzed the CDRH3 region of immunoglobulins and found an amino acid sequence of CDRH3 that is specific to influenza viruses. We are now analyzing the differences in the CDRH3 sequence patterns of antibodies induced in control mice and the original antigenic sin mice by immunoglobulin repertoire analysis.

Academic Significance and Societal Importance of the Research Achievements

抗原原罪現象がワクチン接種により誘導されると、ワクチンの効果が低下する可能性がある。本研究では、マウスをモデルとして抗原原罪現象を再現でき、抗原原罪現象の中で起こっている抗体レパトアを評価することができるようになった。抗体レパトアの継時的な解析により、ワクチン刺激により増加してくる抗体レパトアを検出することができる。抗原原罪現象の中で増加してくる抗体は、望まない免疫応答の一部であり、抗原原罪誘導メカニズムの解析は、安定した感染防御効果を付与できるワクチンの開発に寄与する。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2021 2020 2019

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Updating the influenza virus library at Hokkaido University -It's potential for the use of pandemic vaccine strain candidates and diagnosis2021

    • Author(s)
      Nomura Naoki、Matsuno Keita、Shingai Masashi、Ohno Marumi、Sekiya Toshiki、Omori Ryosuke、Sakoda Yoshihiro、Webster Robert G.、Kida Hiroshi
    • Journal Title

      Virology

      Volume: 557 Pages: 55-61

    • DOI

      10.1016/j.virol.2021.02.005

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Immune profiling of influenza‐specific B‐ and T‐cell responses in macaques using flow cytometry‐based assays2020

    • Author(s)
      Koutsakos Marios、Ishigaki Hirohito、Itoh Yasushi、Kedzierska Katherine et al.
    • Journal Title

      Immunology & Cell Biology

      Volume: 99 Issue: 1 Pages: 97-106

    • DOI

      10.1111/imcb.12383

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Influenza virus infection affects insulin signaling, fatty acid-metabolizing enzyme expressions, and the tricarboxylic acid cycle in mice2020

    • Author(s)
      Ohno Marumi、Sekiya Toshiki、Nomura Naoki、Daito Taku ji、Shingai Masashi、Kida Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1

    • DOI

      10.1038/s41598-020-67879-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inactivated whole virus particle vaccine with potent immunogenicity and limited IL-6 production is ideal for influenza2019

    • Author(s)
      Sekiya T, Mifsud EJ, Ohno M, Nomura N, Sasada M, Fujikura D, Daito T, Shingai M, Ohara Y, Nishimura T, Endo M, Mitsumata R, Ikeda T, Hatanaka H, Kitayama H, Motokawa K, Sobue T, Suzuki S, Itoh Y, Brown LE, Ogasawara K, Kino Y, Kida H
    • Journal Title

      Vaccine

      Volume: 37 Issue: 15 Pages: 2158-2166

    • DOI

      10.1016/j.vaccine.2019.02.057

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Inactivated whole influenza virus particle vaccine showed balanced immunogenicity and safety.2019

    • Author(s)
      Masashi Shingai, Toshiki Sekiya, Marumi Ohno, Naoki Nomura, Takuji Daito, Hiroshi Kida.
    • Organizer
      The 18th Awaji International Forum on Infection and Immunity,
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Priming ability of inactivated whole influenza virus particle vaccine to naive cynomolgus macaques.2019

    • Author(s)
      Masashi Shingai, Naoki Nomura, Toshiki Sekiya, Marumi Ohno, Takuji Daito, Saori Suzuki, Hideaki Ishida, Hirohito Ishigaki, Yasushi Itoh, Kazumasa Ogasawara, Hiroshi Kida.
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Masashi Shingai, Toshiki Sekiya, Marumi Ohno, Naoki Nomura, Hiroshi Kida.2019

    • Author(s)
      Inactivated whole influenza virus particle vaccine with balanced immunogenicity and safety as a radically effectual seasonal influenza vaccine.
    • Organizer
      U.S.-Japan Cooperative Medical Sciences Program. 22nd Acute Respiratory Infections (ARI) Panel Meeting; Viral Diseases.
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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