Development of universal antibody therapy for Ebola hemorrhagic fever

• Project/Area Number: 15K14851
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science
• Research Institution: Hokkaido University
• Principal Investigator: Takada Ayato 北海道大学, 人獣共通感染症リサーチセンター, 教授 (10292062)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 人獣共通感染症 / エボラウイルス / フィロウイルス / 抗体 / 治療法

Outline of Final Research Achievements

Ebolaviruses cause severe hemorrhagic fever (Ebola hemorrhagic fever) in humans and nonhuman primates. Five phylogenetically distinct species are currently known in the genus Ebolavirus and the antigenicity among these ebolavirus species is also largely different. This study attempted to establish procedures to induce neutralizing antibodies cross-reactive to all known ebolavirus species. Our data suggest the possibility that cross-reactive neutralizing antibodies can be induced more efficiently in mice immunized with virus-like particles using an immunosuppressive agent (rapamycin) or mice infected with replication competent vesicular stomatitis virus pseudotyped with ebolavirus glycoprotein than in mice immunized with virus-like particles using a standard adjuvant.

Research Products

• [Int'l Joint Research] National Institute of Health(米国)
• [Journal Article] Taxonomy of the order Mononegavirales: update 2017 (2017)
  • Author(s): Amarasinghe GK, Takada A, et al.
  • Journal Title: Arch. Virol. Volume: 162 (8) Issue: 8 Pages: 2493-2504
  • DOI: 10.1007/s00705-017-3311-7
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] エボラ出血熱に対する治療法および診断法の開発 (2017)
  • Author(s): 古山若呼、吉田玲子、五十嵐学、高田礼人
  • Journal Title: 化学療法の領域 Volume: 33 (5) Pages: 148-155
• [Journal Article] 感染症 現状の問題点と未来への展望 エボラ出血熱 (2017)
  • Author(s): 高田礼人
  • Journal Title: 臨床と微生物 Volume: 45(2) Pages: 165-169
• [Journal Article] Fcγ-receptor IIa-mediated Src signaling pathway is essential for the antibody-dependent enhancement of Ebola virus infection (2016)
  • Author(s): Furuyama W, Marzi A, Carmody AB, Maruyama J, Kuroda M, Miyamoto H, Nanbo A, Manzoor R, Yoshida R, Igarashi M, Feldmann H, Takada A
  • Journal Title: PLoS Pathog. Volume: 12 Issue: 12 Pages: e1006139-e1006139
  • DOI: 10.1371/journal.ppat.1006139
  • NAID: 120005981447
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] エボラ出血熱の診断・治療法開発 ―モノクローナル抗体の活用― (2016)
  • Author(s): 高田礼人
  • Journal Title: 日本臨床 Volume: 74 Pages: 2080-2085
• [Journal Article] エボラ出血熱の予防・治療・診断法開発の現状 (2016)
  • Author(s): 古山若呼、高田礼人
  • Journal Title: ウイルス Volume: 66 Pages: 63-72
  • NAID: 130006882831
• [Journal Article] Discovery of an antibody for pan-ebolavirus therapy (2016)
  • Author(s): Furuyama D, Marzi A, Nanbo A, Haddock E, Maruyama J, Miyamoto H, Igarashi M, Yoshida R, Dr. Noyori O, Feldmann H, Takada A
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 20514-20514
  • DOI: 10.1038/srep20514
  • NAID: 120005906783
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Antibodies against Ebola, Marburg and Lassa - a global collaboration and structural illumination (2017)
  • Author(s): Saphire E, Takada A, et al.
  • Organizer: 9th Internatinal Symposium on Filoviruses
  • Int'l Joint Research
• [Presentation] Ebolavirus --Ecology and antiviral strategies-- (2017)
  • Author(s): Ayato Takada
  • Organizer: 11th Annual Meeting of Korean Society of Zoonosis
  • Invited
• [Presentation] エボラウイルス感染症における新知見 (2017)
  • Author(s): 高田礼人
  • Organizer: 第66回日本感染症学会東日本地方会学術集会
  • Invited
• [Presentation] Neutralization and Antibody-Dependent Enhancement of Ebolavirus (2016)
  • Author(s): Ayato Takada
  • Organizer: 8th International Global Virus Network Meeting
  • Place of Presentation: 札幌コンベンションセンター（札幌市、日本）
  • Year and Date: 2016-10-25
  • Int'l Joint Research / Invited
• [Presentation] Generation of a cross-neutralizing monoclonal antibody against all known ebolavirus species/全てのエボラウイルス種に対する交差中和モノクローナル抗体の作出 (2016)
  • Author(s): Wakako Furuyama, Andrea Marzi, Asuka Nanbo, Elaine Haddock, Junki Maruyama, Hiroko Miyamoto, Manabu Igarashi, Reiko Yoshida, Osamu Noyori, Heinz Feldmann, Ayato Takada
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（札幌市、日本）
  • Year and Date: 2016-10-23
• [Presentation] Ebolavirus Entry into Cells --- Neutralization and Antibody-Dependent Enhancement--- (2016)
  • Author(s): Ayato Takada
  • Organizer: The 15th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路夢舞台国際会議場（淡路市、日本）
  • Year and Date: 2016-09-09
  • Int'l Joint Research / Invited
• [Presentation] A Monoclonal Antibody Neutralizing All Known Ebola Viruses (2016)
  • Author(s): Ayato Takada
  • Organizer: 2016 US-Japan Annual Medical Biodefense Research Symposium Theme: “Ebola And Emerging Pathogens”
  • Place of Presentation: NIH (Rockville, USA)
  • Year and Date: 2016-01-14
  • Int'l Joint Research / Invited
• [Presentation] フィロウイルスの細胞侵入機構 (2015)
  • Author(s): 高田礼人
  • Organizer: 平成27年度 遺伝子病制御研究所研究集会 感染・免疫・炎症・発癌
  • Place of Presentation: 北海道大学医学部 学友会館「フラテ」ホール（札幌市、日本）
  • Year and Date: 2015-12-18
  • Invited
• [Presentation] Ebolavirus: ecology and antiviral strategies (2015)
  • Author(s): Ayato Takada
  • Organizer: 3rd GRF One Health Summit 2015
  • Place of Presentation: Davos Congress Centre (Davos, Switzerland)
  • Year and Date: 2015-10-05
  • Int'l Joint Research / Invited
• [Presentation] エボラウイルスとは (2015)
  • Author(s): 高田礼人
  • Organizer: 第15回日本ハ-イオセーフティ学会総会
  • Place of Presentation: 戸山サンライズ（東京都新宿区、日本）
  • Year and Date: 2015-09-15
  • Invited
• [Presentation] エボラ出血熱 (2015)
  • Author(s): 高田礼人
  • Organizer: 第62回日本実験動物学会総会
  • Place of Presentation: 京都テルサ（京都市、日本）
  • Year and Date: 2015-05-28
  • Invited
• [Presentation] フィロウイルス研究の現状と展望 (2015)
  • Author(s): 高田礼人
  • Organizer: 第33回川内カンファレンス
  • Place of Presentation: 大塚製薬株式会社（徳島市、日本）
  • Year and Date: 2015-04-30
  • Invited