The protective mechanism of an anti-nucleocapsid protein monoclonal antibody against influenza virus infections.

• Project/Area Number: 16K21214
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science; Virology
• Research Institution: Kagoshima University (2018); Kyushu University (2016-2017)
• Principal Investigator: Fujimoto Yoshikazu 鹿児島大学, 農水産獣医学域獣医学系, 准教授 (20613631)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: インフルエンザウイルス / トランスジェニックマウス / 抗体 / 感染抵抗性 / 感染防御抗体

Outline of Final Research Achievements

The purpose of this research subject was elucidation of antiviral mechanism of an anti-nucleocapsid protein (NP) antibody against influenza virus infections. It has been known that one of antiviral mechanisms of non-neutralizing antibodies is antibody-dependent cellular cytotoxicity (ADCC) and / or complement-dependent cellular cytotoxicity (CDC) activity. Transgenic (TG) mice expressing an anti-NP monoclonal antibody with mutations at several sites that are important for ADCC and CDC activities were generated, and experimental infections with an influenza virus were performed. As compared to wild type mice, TG mice expressing the ADCC / CDC activity-deficient antibody showed resistance to the viral infection. These results suggested that a different mechanism from ADCC and CDC activities may be responsible for protective effects of anti-NP antibodies against influenza virus infection.

Academic Significance and Societal Importance of the Research Achievements

将来発生する鳥インフルエンザの原因ウイルス亜型を予想することは困難である。亜型を問わず感染防御効果を示す万能ワクチンは、緊急時のウイルス感染拡大防止策の有効な手段となることや、罹患家禽と密に接する防疫従事者への感染予防に利用されることが期待される。ヌクレオカプシド蛋白質（NP）には、インフルエンザウイルスに共通した抗原領域が多く保存されているため、万能ワクチンの標的蛋白質として適しているが、その感染防御機序は明らかにはされてない。本研究成果は、抗NP抗体による感染防御機序に関する新たな知見を得られた点に学術的意義があり、NPを標的とした万能ワクチン開発に繋がる重要な知見であると考えられる。

Research Products

• [Journal Article] Antiviral effects against influenza A virus infection by a short hairpin RNA targeting the non-coding terminal region of the viral nucleoprotein gene (2019)
  • Author(s): Fujimoto Y, Kyogoku K, Takeda K, Ozaki K, Yamamoto S, Suyama H, Ono E.
  • Journal Title: Journal of Veterinary Medical Science Volume: 81 Issue: 3 Pages: 383-388
  • DOI: 10.1292/jvms.18-0436
  • NAID: 130007614053
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Open Access
• [Journal Article] Cross-protective potential of anti-nucleoprotein human monoclonal antibodies against lethal influenza A virus infection (2016)
  • Author(s): Fujimoto Y., Tomioka Y., Takakuwa H., Uechi GI., Yabuta T., Ozaki K., Suyama H., Yamamoto S., Morimatsu M., Mai L.Q., Yamashiro T., Ito T., Otsuki K., Ono E.
  • Journal Title: Journal of General Virology Volume: 97 Issue: 9 Pages: 2104-2116
  • DOI: 10.1099/jgv.0.000518
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] ヒト由来抗体発現トランスジェニックマウスを利用した抗NPモノクローナル抗体におけるインフルエンザウイルス感染防御能の解析 (2016)
  • Author(s): 藤本佳万、尾崎絹代、上地玄一郎、高桑弘樹、富岡幸子、藪田淑予、陶山晴香、山本沙代、森松正美、伊藤壽啓、大槻公一、Le Quynh Mai、山城哲、小野悦郎
  • Organizer: 第３４回九州実験動物研究会
  • Place of Presentation: 産業医科大学（北九州市）
  • Year and Date: 2016-10-29
• [Presentation] Anti-nucleocapsid protein antibody is sufficient to confer resistance to lethal infection with influenza A viruses of several subtypes in transgenic mice (2016)
  • Author(s): Fujimoto Y., Tomioka Y., Takakuwa H., Uechi GI., Yabuta T., Ozaki K., Suyama H., Yamamoto S., Morimatsu M., Mai L.Q., Yamashiro T., Ito T., Otsuki K., Ono E.
  • Organizer: International Symposium for Southern China Laboratory Animal Sciences
  • Place of Presentation: 中華人民共和国・広東省
  • Year and Date: 2016-08-21
  • Int'l Joint Research / Invited