Establishment of monoclonal antibodies that neutralize all HA subtypes of influenza A viruses

• Project/Area Number: 26850180
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science
• Research Institution: Kyoto University (2015); The University of Tokyo (2014)
• Principal Investigator: MURAMOTO Yukiko 京都大学, ウイルス研究所, 特定研究員 (70436567)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: インフルエンザウイルス

Outline of Final Research Achievements

The aim of the study is to establish monoclonal antibodies which recognize all subtypes of influenza A virus HAs. First, we assessed virus-like particles of HIV Gag which possess stalk region of HA protein as an immunogen. HA stalk protein was detected on the surface of Gag virus-like particles generated by the expression of both HIV Gag and HA stalk in mammalian cells. However, we found that the amount of the virus-like particles was not sufficient for immunization. Then, we immunized mice with purified influenza A virus particles. After the fusion process of spleen cells with myeloma cells, antibodies against HA have been screened using several subtypes of HA proteins.

Research Products

• [Journal Article] An Ultrasensitive Mechanism Regulates Influenza Virus-Induced Inflammation. (2015)
  • Author(s): Shoemaker JE, Fukuyama S, Eisfeld AJ, Zhao D, Kawakami E, Sakabe S, Maemura T, Gorai T, Katsura H, Muramoto Y, Watanabe S, Watanabe T, Fuji K, Matsuoka Y, Kitano H, Kawaoka Y
  • Journal Title: PLoS Pathogens Volume: 11 Issue: 6 Pages: e1004856-e1004856
  • DOI: 10.1371/journal.ppat.1004856
  • NAID: 120006987004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An ultrasensitive mechanism regulates influenza virus-induced inflammation (2015)
  • Author(s): Shoemaker JE, Fukuyama S, Eisfeld AJ, Zhao D, Kawakami E, Sakabe S, Maemura T, Gorai T, Katsura H, Muramoto Y, Watanabe S, Watanabe T,,Fuji K, Matsuoka Y, Kitano H, Kawaoka Y.
  • Journal Title: PLoS Pathog. Volume: 印刷中
  • NAID: 120006987004
  • Peer Reviewed / Open Access
• [Journal Article] Disease severity is associated with differential gene expression at the early and late phases of infection in nonhuman primates infected with different H5N1 highly pathogenic avian influenza viruses. (2014)
  • Author(s): Muramoto Y, Shoemaker JE, Le MQ, Itoh Y, Tamura D, Sakai-Tagawa Y, Imai H, Uraki R, Takano R, Kawakami E, Ito M, Okamoto K, Ishigaki H, Mimuro H, Sasakawa C, Matsuoka Y, Noda T, Fukuyama S, Ogasawara K, Kitano H, Kawaoka Y.
  • Journal Title: Journal of Virlogy Volume: 88(16) Issue: 16 Pages: 8981-8997
  • DOI: 10.1128/jvi.00907-14
  • Peer Reviewed / Open Access
• [Presentation] 高病原性H5N1鳥インフルエンザウイルス感染による重症化には感染初期のISGsの発現が関与する (2015)
  • Author(s): 村本裕紀子
  • Organizer: Fourth Negative Strand Virus - Japan Symposium
  • Place of Presentation: ラグナガーデンホテル（沖縄県宜野湾市）
  • Year and Date: 2015-01-19 – 2015-01-21
• [Presentation] 高病原性H5N1鳥インフルエンザウイルスに感染したカニクイザルの宿主応答 (2014)
  • Author(s): 村本裕紀子、Jason E. Shoemaker、Le Thi Quynh Mai、 伊藤靖、田村大輔、坂井（田川）優子、今井博貴、岡本貴世子、石垣宏仁、小笠原一誠、北野宏明、河岡義裕
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] 高病原性H5N1鳥インフルエンザウイルスに感染したカニクイザルの宿主応答 (2014)
  • Author(s): 村本裕紀子、Jason E. Shoemaker、Le Thi Quynh Mai、 伊藤靖、田村大輔、坂井（田川）優子、今井博貴、岡本貴世子、石垣宏仁、小笠原一誠、北野宏明、河岡義裕
  • Organizer: 第157回日本獣医学会学術集会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2014-09-09 – 2014-09-12