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

• Project/Area Number: 18K07135
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: Hokkaido 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: ¥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。

Research Products

• [Journal Article] Updating the influenza virus library at Hokkaido University -It's potential for the use of pandemic vaccine strain candidates and diagnosis (2021)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Immune profiling of influenza‐specific B‐ and T‐cell responses in macaques using flow cytometry‐based assays (2020)
  • 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
  • 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 mice (2020)
  • 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
  • Peer Reviewed
• [Journal Article] Inactivated whole virus particle vaccine with potent immunogenicity and limited IL-6 production is ideal for influenza (2019)
  • 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
  • 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,
  • 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
• [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.
  • Int'l Joint Research / Invited