Research on protection against influenza viral infection using human monoclonal antibody

• Project/Area Number: 23790660
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hygiene
• Research Institution: Osaka Prefecture University
• Principal Investigator: YASUGI Yasugi 大阪府立大学, 大学院・生命環境科学研究科, 助教 (40589008)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: インフルエンザウイルス / ヒト型抗体

Research Abstract

Our established human monoclonal antibody (HuMAb) 5A7 recognized a highly conserved regionof hemagglutinin (HA) in influenza B viruses (FluB). 5A7 broadly neutralized FluB and showed significant therapeutic efficacy in mice. These results indicate that 5A7 provides insight for the development of a universal vaccine against FluB. Also we studied the diversity of A(H1N1)pdm09 using neutralizing HuMAb 5E4 recognizing antigenic site Sb in the HA protein of A(H1N1)pdm09. Neutralization titers were significantly reduced against 5E4 in the 2010/11 compared with the 2009/10 samples. Sequences in Sb were being positively selected between 2009/10 and 2010/11. Variants in the antigenic site Sb increased significantly worldwide from GenBank, indicating that the antigenic variants in Sb are likely to be in global circulation currently.

Research Products

• [Journal Article] Human Monoclonal Antibodies Broadly Neutralizing against Influenza B Virus (2013)
  • Author(s): Yasugi M. Kubota-Koketsu R, Yamashita A, Kawashita N, Du A, 他9名
  • Journal Title: PLoS PATHOGENS Volume: 9(2)
  • Peer Reviewed
• [Journal Article] Human monoclonal antibodies broadly neutralizing against influenza B virus. (2013)
  • Author(s): Yasugi, M., Kubota-Koketsu, R., Yamashita, A., Kawashita, N., Du, A., Sasaki, T., Nishimura, M., Misaki, R., Kuhara, M., Boonsathorn, N., Fujiyama, K., Okuno, Y., Nakaya, T., and Ikuta, K.
  • Journal Title: PLoS Pathog. Volume: 9 Issue: 2 Pages: e1003150-e1003150
  • DOI: 10.1371/journal.ppat.1003150
  • Peer Reviewed
• [Journal Article] Tropism of pandemic 2009 H1N1 influenza A virus. (2012)
  • Author(s): Ramadhany, R., Yasugi, M., Nakamura, S., Daidoji, T., Watanabe, Y., Takahashi, K., Ikuta, K., and Nakaya, T.
  • Journal Title: Front. Microbiol. Volume: 3 Pages: 128-128
  • DOI: 10.3389/fmicb.2012.00128
  • Peer Reviewed
• [Journal Article] Frequency of D222G and Q223R hemagglutinin mutants of pandemic (H1N1) 2009 influenza virus in Japan between 2009 and 2010 (2012)
  • Author(s): Yasugi M, Nakamura S, Daidoji T, Kawashita N, Ramadhany R, Yang CS, Yasunaga T, Iida T, Horii T, Ikuta K, Takahashi K, Nakaya T
  • Journal Title: PLoS One Volume: 7 Issue: 2 Pages: e30946-e30946
  • DOI: 10.1371/journal.pone.0030946
  • Peer Reviewed
• [Presentation] インフルエンザウイルスに対して広い反応性を示すヒト型モノクローナル抗体の分離 (2012)
  • Author(s): 金井祐太、安木真世、潘洋、Boonsathom N、小野健一郎、生田和良
  • Organizer: 第60回日本ウイルス学会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-15
• [Presentation] A型インフルエンザウイルス感染によるムチン型糖転移酵素GALNT3の発現制御機序と意義の解析 (2012)
  • Author(s): 中村祥子、堀江真行、安木真世、奥崎大介、牧野晶子、本田知之、朝長啓造
  • Organizer: 第60回日本ウイルス学会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-14
• [Presentation] SPYMEGを用いた抗ウイルス完全ヒト型中和抗体の作成～評価例 (2012)
  • Author(s): 安木真世
  • Organizer: 第60回日本ウイルス学会
  • Place of Presentation: 大阪(招待講演)
  • Year and Date: 2012-11-13
• [Presentation] 高病原性鳥インフルエンザウイルスH5N1はヒト呼吸器上皮細胞に対して広いトロピズムを示す (2012)
  • Author(s): 大道寺智、Ibrahim MS、渡邊洋平、安木真世、丸山央峰、益田泰輔、新井史人、大場誠介、本田文江、生田和良、中屋隆明
  • Organizer: 第60回日本ウイルス学会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-13
• [Presentation] High-throughput amplicon sequencing analysis of pandemic(H1N1)2009 influenza virus in Japan between 2009 and 2010 (2012)
  • Author(s): Ramadhany R、安木真世、中村昇太、大道寺智、渡邊洋平、高橋和郎、生田和良、中屋隆明
  • Organizer: 第60回日本ウイルス学会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-13
• [Presentation] Broadly neutralizing monoclonal antibodies against influenza viruses (2012)
  • Author(s): 潘洋、安木真世、金 井 祐 太 、Boonsathorn N、小野健一郎、生田和良
  • Organizer: 第60回日本ウイルス学会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-13
• [Presentation] Human Monoclonal Antibodies Broadly Protective against Influenza B Virus (2012)
  • Author(s): Yasugi M, Koketsu R, Yamashita A, Kawashita N, Du A, Kuhara M, Fujiyama K, Okuno Y, Ikuta K
  • Organizer: The 11th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Hyogo
  • Year and Date: 2012-09-12
• [Presentation] SPYMEGを用いた抗ウイルス完全ヒト型中和抗体の作製～評価例 (2012)
  • Author(s): 安木真世
  • Organizer: 第60回日本ウイルス学会
  • Place of Presentation: 大阪
  • Invited
• [Presentation] Human Monoclonal Antibodies Broadly Protective against Influenza B Virus (2012)
  • Author(s): Yasugi M, Koketsu R, Yamashita A, Kawashita N, Du A, Kuhara M, Fujiyama K, Okuno Y, Ikuta K
  • Organizer: The 11th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 兵庫
• [Presentation] Use of a human monoclonal antibody to detect emerging antigenic variants at the antigenic site sb in pandemic(H1N1)2009 influenza virus in Japan (2011)
  • Author(s): Yasugi M
  • Organizer: Joint International Tropical Medicine Meeting 2011
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2011-12-02
• [Presentation] Epitope mapping of human monoclonal antibody neutralizing 2009 pandemic influenza A virus (2011)
  • Author(s): Yasugi M, Du A, Kawashita N, Koketsu R, Nakaya T, Kuhara M, Boonsathorn N, Sawanpanyalert P, Ikuta K
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Sapporo
  • Year and Date: 2011-09-13
• [Presentation] 2009 pandemic influenza A(H1N1) viruses with D222G and Q223R hemagglutinin mutations exist as a minor population in human upper airways (2011)
  • Author(s): Nakaya T, Yasugi M, Nakamura S, Daidoji T, Ramadhany R, Yang CS, Yasunaga T, Iida T, Horii T, Ikuta K, Takahashi K
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Sapporo
  • Year and Date: 2011-09-13
• [Presentation] Upregulation of GALNT3 at the early stage of influenza A virus infection through the miRNA pathway (2011)
  • Author(s): Horie M, Yasugi M, Okuzaki D, Honda T, Tomonaga K
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Sapporo
  • Year and Date: 2011-09-13
• [Presentation] Wide-ranged cell tropism of Asian-H5N1 viruses in human airway epithelial cells (2011)
  • Author(s): Daidoji T, Ibrahim MS, Watanabe Y, Yasugi M, Yang CS, Ikuta K, Nakaya T
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Sapporo
  • Year and Date: 2011-09-13
• [Presentation] Epitope mapping of human monoclonal antibody neutralizing 2009 pandemic influenza A virus
  • Author(s): Yasugi M, Du A, Kawashita N, Koketsu R, Nakaya T, Kuhara M, Boonsathom N, Sawanpanyalert P, Ikuta K
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: 札幌
• [Presentation] Use of a human monoclonal antibody to detect emerging antigenic variants at the antigenic site Sb in pandemic (H1N1) 2009 influenza virus in Japan
  • Author(s): Yasugi M
  • Organizer: Joint International Tropical Medicine Meeting 2011
  • Place of Presentation: バンコク
• [Presentation] 2009 pandemic influenza A (H1N1) viruses with D222G and Q223R hemagglutinin mutations exist as a minor population in human upper airways
  • Author(s): Nayaka T, Yasugi M, Nakamura S, Daidoji T, Ramadhany R, Yang CS, Yasunaga T, Iida T, Horii T, Ikuta K, Takahashi K
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: 札幌
• [Presentation] Upregulation of GALNT3 at the early stage of influenza a virus infection through the miRNA pathway
  • Author(s): Horie M, Yasugi M, Okuzaki D, Honda T, Tomonaga K
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: 札幌
• [Presentation] Wide-ranged cell tropism of Asian-H5N1 viruses in hunman airway epithelial cells
  • Author(s): Daidoji T, Ibrahim MS, Watanabe Y, Yasugi M, Yang CS, Ikuta K, Nakaya T
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: 札幌
• [Remarks]
  • URL: http://virology.biken.osaka-u.ac.jp/index.php
• [Patent(Industrial Property Rights)] Human Monoclonal Antibodies Broadly Protective against Influenza B Virus (2013)
  • Inventor(s): 安木真世、藤山和仁、生田和良、久原基樹、Boon-Long J、纐纈律子
  • Industrial Property Rights Holder: (株)医学生物学研究所、(財)阪大微生物病研究会、タイ王国健康保健省医科学局、大阪大学
  • Filing Date: 2013-01-31
• [Patent(Industrial Property Rights)] Human Monoclonal Antibodies Broadly Protective Against Influenza B Virus (2013)
  • Inventor(s): 安木真世、藤山和仁、生田和良、久原基樹、纐纈律子 他1名
  • Industrial Property Rights Holder: MBL、阪大微生物病研究会、タイ王国NIH、大阪大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-01-31
  • Overseas