Antibody therapy against novel influenza virus infection using anImmunosuppressed non-human primate model

• Project/Area Number: 22390076
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: ITOH Yasushi 滋賀医科大学, 医学部, 准教授 (90324566)
• Co-Investigator(Kenkyū-buntansha): OGASAWARA Kazumasa 滋賀医科大学, 医学部, 教授 (20169163) ; ITO Mutsumi 東京大学, 医科学研究所, 技術職員 (80573906)
• Co-Investigator(Renkei-kenkyūsha): 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): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2012: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2011: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2010: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
• Keywords: インフルエンザウイルス / 霊長類モデル / 抗体医薬 / 免疫抑制 / ペプチド / 免疫不全 / インフルエンザ / 抗体療法

Research Abstract

The purpose of this study is development of anti-influenza virus drugs that are effective under the immunocompromised condition.We developed human-mouse chimeric anti-influenza virus hemagglutinin antibody with neutralizing activity. Administration of the antibody to immunosuppressed cynomolgus macaques improved survival rates in highly pathogenic avian influenza virus infection, whereas immunosuppressed macaques without the treatment showed severe symptoms. It is expected that the therapy with the developed anti-hemagglutinin antibody would be effective in immunocompromised influenza patients as confirmed in the immunosuppressed macaquemodel.

Research Products

• [Journal Article] Efficacy of repeated intravenous injection of peramivir against influenza A (H1N1) 2009 virus infection in immunosuppressed mice (2013)
  • Author(s): Kitano M, Kodama M, Itoh Y, Kanazu T, Kobayashi M, Yoshida R, Sato A
  • Journal Title: Antimicrobial Agents and Chemotherapy Volume: Vol.57 Issue: 5 Pages: 2286-2294
  • DOI: 10.1128/aac.02324-12
  • Peer Reviewed
• [Journal Article] Memory immune responses against pandemic (H1N1) 2009 influenza virus induced by a whole particle vaccine in ynomolgus monkeys carrying Mafa-A*052:02 (2012)
  • Author(s): Arikata M, Itoh Y, Okamatsu M, Maeda T, Shiina T, Tanaka K, Suzuki S, Nakayama M, Sakoda Y, Ishigaki H, Takada A, Ishida H, Soda K, Pham VL, Tsuchiya H, Nakamura S, Torii R, Shimizu T, Inoko H, Ohkubo I, Kida H, Ogasawara K
  • Journal Title: PLos ONE Volume: 7 Issue: 5 Pages: e37220-e37220
  • DOI: 10.1371/journal.pone.0037220
  • Peer Reviewed
• [Journal Article] Efficacy of single intravenous injection of peramivir against influenza B virus infection in ferrets and cynomolgus macaques (2011)
  • Author(s): Kitano M, Itoh Y, Kodama M, Ishigaki H, Nakayama M, Ishida H, Baba K, Noda T, Sato K, Nihashi Y, Kanazu T, Yoshida R, Torii R, Sato A, Ogasawara K
  • Journal Title: Antimicrobial Agents and Chemotherapy Volume: Vol.55 Issue: 11 Pages: 4961-4970
  • DOI: 10.1128/aac.00412-11
  • Peer Reviewed
• [Journal Article] Establishment of a cynomolgus macaque model of influenza B virus infection (2010)
  • Author(s): Kitano M, Itoh Y, Kodama M, Ishigaki H, Nakayama M, Nagata T, Ishida H, Tsuchiya H, Torii R, Baba K, Yoshida R, Sato A, Ogasawara K
  • Journal Title: Virology Volume: Vol. 407 Issue: 2 Pages: 178-184
  • DOI: 10.1016/j.virol.2010.08.006
  • Peer Reviewed
• [Journal Article] Establishment of a cynomolgus macaque model of influenza B virus infection (2010)
  • Author(s): Kitano M, Iton Y, et al.
  • Journal Title: Virology Volume: VOL.470 Pages: 178-184
  • Peer Reviewed
• [Presentation] 免疫抑制カニクイザルを用いたパンデミックH1N1亜型インフルエンザウイルスの病原性の解析 (2013)
  • Author(s): 伊藤靖、Pham Van Loi、仲山美沙子、七戸新太郎、石垣宏仁、有方雅彦、石田英晃、北川直子、岡松正敏、迫田義博、喜田宏、小笠原一誠
  • Organizer: 第27回インフルエンザ研究者交流の会シンポジウム
  • Place of Presentation: 北海道大学(北海道)
• [Presentation] 免疫抑制カニクイザルを用いたパンデミックH1N1亜型インフルエンザウイルスの病原性の解析 (2013)
  • Author(s): 伊藤靖 他
  • Organizer: 第２７回インフルエンザ研究者交流の会シンポジウム
  • Place of Presentation: 北海道大学（北海道）
• [Presentation] Therapeutic efficacy of a human-mouse chimeric anti-H5 hemagglutinin antibody on lethal H5N1 highly pathogenic avian influenza virus infection in cynomolgus macaques (2012)
  • Author(s): Itoh Y, Ishigaki H, Nakayama M, Ishida H, Ogasawara K.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2012-12-07
• [Presentation] An inactivated whole particle vaccine induced memory immune responses against pandemic (H1N1) 2009 influenza virus in cynomolgus monkeys carrying Mafa-A1*052:02 (2012)
  • Author(s): Itoh Y, Arikata M, Okamatsu M, Nakayama M, Sakoda Y, Ishigaki H, Takada A, Ishida H, Soda K, Pham VL, Kida H, Ogasawara K.
  • Organizer: 第16回日本ワクチン学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2012-11-18
• [Presentation] Influenza virus peptides specifically bound to cynomolgus macaque major histocompatibility complex class I Mafa-A1*5202 (2011)
  • Author(s): Itoh Y, Arikata M, Ishigaki H, Nakayama M, Ishida H, Ogasawara
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ(千葉県)
  • Year and Date: 2011-11-29
• [Presentation] Influenza virus peptides specifically bound to cynomolgus macaque major histocompatibility complex class I Mafa-Al^*5202 (2011)
  • Author(s): Itoh Y, et al
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ(千葉県)
  • Year and Date: 2011-11-29
• [Presentation] Identification of pandemic influenza virus NP peptides bound to cynomolgus macaque MHC class I Mafa-A1*5202 and stimulating CTL responses (2011)
  • Author(s): Itoh Y, Arikata M, Maeda T, Shiina T, Ishigaki H, Takada A, Okamatsu M, Sakoda Y, Nakayama M, Kida H, Ogasawara K
  • Organizer: XV International Congress of Virology
  • Place of Presentation: 札幌コンベンションセンター(北海道)
  • Year and Date: 2011-09-15
• [Presentation] Identification of pandemic influenza virus NP peptides bound to cynomolgus macaque MHC class I Mafa-Al^*5202 and stimulating CTL responses (2011)
  • Author(s): Itoh Y, et al
  • Organizer: XV International Congress of Virology
  • Place of Presentation: 札幌コンベンションセンター(北海道)
  • Year and Date: 2011-09-15
• [Presentation] An inactivated whole particle vaccine from a non-pathogenic virus library confers protective immunity against H1N1 pandemic influenza virus more effectively than dose a split vaccine in cynomolgus macaques (2010)
  • Author(s): Itoh Y, Okamatsu M, Nakayama M, Sakoda Y, Ishigaki H, Ishida H, Arikata M, Pham, VL, Soda K, Kida H, Ogasawara K
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸国際展示場 (兵庫県)
  • Year and Date: 2010-08-24
• [Presentation] An inactivated whole particle vaccine from a non-pathogenic virus library confers protective immunity against H1N1 pandemic influenza virus more effectively than dose a split vaccine in cynomolgus macaques. (2010)
  • Author(s): Itoh Y, et al.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-08-24
• [Presentation] カニクイザルモデルを用いたパンデミック(H1N1)2009インフルエンザウイルス感染による炎症反応の解析 (2010)
  • Author(s): 伊藤靖、石垣宏仁、仲山美沙子、小笠原一誠、河岡義裕
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 京王プラザホテル新宿(東京都)
  • Year and Date: 2010-04-27
• [Presentation] カニクイザルモデルを用いたパンデミック(H1N1)2009インフルエンザウイルス感染による炎症反応の解析 (2010)
  • Author(s): 伊藤靖, 他
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 2010-04-27
• [Presentation] Therapeutic efficacy of a human-mouse chimeric anti-H5 hemagglutinin antibody on lethal H5N1 highly pathogenic avian influenza virus infection in cynomolgus macaques
  • Author(s): Yasushi Itoh, et al.
  • Organizer: 第４１回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場（兵庫県）
• [Presentation] An inactivated whole particle vaccine induced memory immune responses against pandemic (H1N1) 2009 influenza virus in cynomolgus monkeys carrying Mafa-A1*052:02
  • Author(s): Yasushi Itoh, et al.
  • Organizer: 第１６回日本ワクチン学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Remarks]
  • URL: http://www.shiga-med.ac.jp/~hqpatho2/
• [Remarks] 滋賀医科大学疾患制御病理学研究業績
  • URL: http://www.shiga-med.ac.jp/~hqpatho2/publications.html