Basic study on novel vaccine strategy for avian influenza

2013 Fiscal Year Final Research Report

• Project/Area Number: 21380187
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied veterinary science
• Research Institution: The University of Tokyo
• Principal Investigator: HORIMOTO Taisuke 東京大学, 農学生命科学研究科, 准教授 (00222282)
• Project Period (FY): 2009-04-01 – 2014-03-31
• Keywords: 人獣共通感染症 / 鳥インフルエンザ / ワクチン

Research Abstract

Avian influenza viruses such as H5N1 virus possess a pandemic potential. Possible emergence of drug-resistant viruses emphasizes the importance of influenza vaccines. However, low efficacy of the current inactivated vaccines and limited safety of the live attenuated vaccines provide a need for novel vaccine strategy against influenza. Here I generated replication-incompetent viruses, which infect cells once followed by expression of viral preventive antigens in animals, leading to a new vaccine with higher efficacy and safety. To this end, I produced replication-incompetent viruses such as M2-, NS2-, NA-, or HA-deletion construct by reverse genetics. These can replicate in each protein-expressed cell cultures, followed by intranasal inoculation into mice to evaluate their safety and vaccine efficacy. Conclusively replication-incompetent virus with defective HA fusion is promising as an alternative influenza vaccine.

Research Products

• [Journal Article] Physical interaction between bovine viral diarrhea virus nonstructural protein 4A and adenosine deaminase acting on RNA (ADAR) (2014)
  • Author(s): Mohamed YM, Bangphoomi N, Yamane D, Suda Y, Kato K, Horimoto T, Akashi H
  • Journal Title: Arch Virol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Serological evidence of infection of dogs with human influenza viruses in Japan (2014)
  • Author(s): Horimoto T, Gen F, Murakami S, Iwatsuki-Horimoto K, Kato K, Akashi H, Hisasue M, Sakaguchi M, Kawaoka Y, Maeda K
  • Journal Title: Vet Rec Volume: 174 Pages: 96
  • DOI: 10.1136/vr.101929
  • Peer Reviewed
• [Journal Article] A cell-based high-throughput screening system for influenza A viral RNA transcription/replication inhibitors (2013)
  • Author(s): Ozawa, M, Shimojima M, Goto H, Watanabe S, Hatta Y, Kiso M, Furuta Y, Horimoto T, Peters NR, Hoffmann MF, Kawaoka Y
  • Journal Title: Sci Rep Volume: 3 Pages: 1106
  • DOI: 10.1038/srep01106
  • Peer Reviewed
• [Journal Article] Attenuation of an influenza A virus due to alteration of its hemagglutinin-neuraminidase functional balance in mice (2013)
  • Author(s): Gen F, Yamada S, Kato K, Akashi H, Kawaoka Y, Horimoto T
  • Journal Title: Arch Virol Volume: 158 Pages: 1003-1011
  • DOI: 10.1007/s00705-012-1577-3
  • Peer Reviewed
• [Journal Article] Enhanced growth of influenza vaccine seed viruses in Vero cells mediated by broadening the optimal pH range for virus membrane fusion (2012)
  • Author(s): Murakami S, Horimoto T, Ito M, Takano R, Katsura K, Shimojima M, Kawaoka Y
  • Journal Title: J Virol Volume: 86 Pages: 1405-1410
  • DOI: 10.1128/JVI.06009-11
  • Peer Reviewed
• [Journal Article] A replication-incompetent virus possessing an uncleavable hemagglutinin as an influenza vaccine (2012)
  • Author(s): Katsura H, Iwatsuki-Horimoto K, Fukuyama S, Watanabe S, Sakabe S, Hatta Y, Murakami S, Shimojima M, Horimoto T, Kawaoka Y
  • Journal Title: Vaccine Volume: 30 Pages: 6027-6033
  • DOI: 10.1016/j.vaccine.2012.07.059
  • Peer Reviewed
• [Journal Article] Effect of an asparagine-to-serine mutation at position 294 in neuraminidase on the pathogenicity of highly pathogenic H5N1 influenza A virus (2011)
  • Author(s): Kiso M, Ozawa M, Le MQ, Imai H, Takahashi K, Kakugawa S, Noda T, Horimoto T, Kawaoka Y
  • Journal Title: J Virol Volume: 85 Pages: 860-866
  • DOI: 10.1128/JVI.00047-11
  • Peer Reviewed
• [Journal Article] Highly pathogenic avian influenza virus infection in feral raccoons, Japan (2011)
  • Author(s): Horimoto T, Maeda K, Murakami S, Kiso M, Iwatsuki-Horimoto K, Sashika M, Ito T, Suzuki K, Yokoyama M, and Kawaoka Y
  • Journal Title: Emerg Infect Dis Volume: 17 Pages: 714-717
  • DOI: 10.3201/eid1704.101604
  • Peer Reviewed
• [Journal Article] インフルエンザワクチン (2011)
  • Author(s): 堀本泰介
  • Journal Title: 日生研だより Volume: 57 Pages: 64-69
• [Journal Article] A cross-reactive neutralizing monoclonal antibody protects mice from H5N1 and pandemic (H1N1) 2009 virus infection (2010)
  • Author(s): Sakabe S, Iwatsuki-Horimoto K, Horimoto T, Nidom CA, Le QM, Takano R, Kubota-Koketsu R, Okuno Y, Ozawa M, Kawaoka Y
  • Journal Title: Antiviral Res Volume: 88 Pages: 249-255
  • DOI: 10.1016/j.antiviral.2010.09.007
  • Peer Reviewed
• [Journal Article] The HA and NS genes of human H5N1 influenza A virus contribute to high virulence in ferrets (2010)
  • Author(s): Imai H, Shinya K, Takano R, Kiso M, Muramoto Y, Sakabe S, Murakami S, Ito M, Yamada S, Le MT, Nidom CA, Sakai-Tagawa Y, Takahashi K, Omori Y, Noda T, Shimojima M, Kakugawa S, Goto H, Iwatsuki-Horimoto K, Horimoto T, Kawaoka Y
  • Journal Title: PloS Pathog Volume: 6 Pages: e1001106
  • DOI: 10.1371/journal.ppat.1001106
  • Peer Reviewed
• [Journal Article] Animal models to study influenza virus pathogenesis and control (2010)
  • Author(s): Haga T, Horimoto T
  • Journal Title: The Open Antimicrobial Agents Journal Special Issues Pages: 15-21
  • Peer Reviewed
• [Journal Article] Pandemic influenza (2010)
  • Author(s): Horimoto T
  • Journal Title: The Open Antimicrobial Agents Journal Special Issues Pages: 9-14
  • Peer Reviewed
• [Journal Article] The MAPKactivated kinase RSK2 plays a role in innate immune responses to influenza virus infection (2009)
  • Author(s): Kakugawa S, Shimojima M, Goto H, Horimoto T, Oshimori N, Neumann G, Yamamoto T, Kawaoka Y
  • Journal Title: J Virol Volume: 83 Pages: 210-2517
  • DOI: 10.1128/JVI.02416-08
  • Peer Reviewed
• [Journal Article] Incorporation of Influenza A virus genome segments does not absolutely require wild-type sequences (2009)
  • Author(s): Fujii K, Ozawa M, Iwatsuki- Horimoto K, Horimoto T, Kawaoka Y
  • Journal Title: J Gen Virol Volume: 90 Pages: 1734-1740
  • DOI: 10.1099/vir.0.010355-0
  • Peer Reviewed
• [Journal Article] H5N1インフルエンザワクチン (2009)
  • Author(s): 村上晋, 堀本泰介, 河岡義裕
  • Journal Title: メディカルバイオ Volume: 6 Pages: 55-59
• [Presentation] A型インフルエンザウイルスのHA 遺伝子非コード領域の機能解析 (2013)
  • Author(s): 光井英晃, 玄文宏, 村上晋, 須田遊人, 加藤健太郎, 明石博臣, 河岡義裕, 堀本泰介
  • Organizer: 第61回日本ウイルス学会
  • Place of Presentation: 神戸国際会議場(神戸)
  • Year and Date: 2013-11-11
• [Presentation] A型インフルエンザウイルス(H1N1)のHA遺伝子非コード領域の機能解析 (2013)
  • Author(s): 光井英晃, 玄文宏, 須田遊人, 加藤健太郎, 明石博臣, 河岡義裕, 堀本泰介
  • Organizer: 第156回日本獣医学会
  • Place of Presentation: 岐阜大学(岐阜)
  • Year and Date: 2013-09-20
• [Presentation] 野生イノシシにおけるA型インフルエンザウイルス感染 (2013)
  • Author(s): 前田健, 下田宙, 米満研三, 寺田豊, 野口慧多, 高野愛, 小寺祐二, 竹田努, 小野文子, 高井伸二, 吉川泰弘, 岩附研子, 河岡義裕, 堀本泰介
  • Organizer: 第156回日本獣医学会
  • Place of Presentation: 岐阜大学(岐阜)
  • Year and Date: 2013-09-20
• [Presentation] わが国の哺乳動物におけるインフルエンザウイルス感染 (2012)
  • Author(s): 堀本泰介, 玄文宏, 附研子, 木曽真紀, 村上晋, 加藤健太郎, 久末正晴, 阪口雅弘, 明石博臣, 伊藤壽啓, 河岡義裕, 前田健
  • Organizer: 第60回日本ウイルス学会総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2012-11-14
• [Presentation] NA発現細胞で高い増殖性を示すインフルエンザウイルスHA変異株の性状解析 (2012)
  • Author(s): 玄文宏, 山田晋弥, 岩附研子, 加藤健太郎, 明石博臣, 河岡義裕, 堀本泰介
  • Organizer: 第60回日本ウイルス学会総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2012-11-14
• [Presentation] わが国の哺乳動物におけるインフルエンザウイルス感染 (2012)
  • Author(s): 堀本泰介, 玄文宏, 岩附研子, 加藤健太郎, 久末正晴, 阪口雅弘, 明石博臣, 伊藤壽啓, 前田健
  • Organizer: 第154回日本獣医学会
  • Place of Presentation: 岩手大学(盛岡)
  • Year and Date: 2012-09-15
• [Presentation] A replicationincompetent virus possessing an uncleavable HA as an influenza vaccine (2011)
  • Author(s): Katsura H, Iwatsuki-Horimoto K, Fukuyama S, Watanabe S, Sakabe S, Horimoto T, Kawaoka Y
  • Organizer: XVth International Congress of Virology国際ウイルス学会
  • Place of Presentation: 札幌コンベンションセンター(北海道)
  • Year and Date: 2011-09-13
• [Presentation] 国内のペット犬におけるインフルエンザウイルス感染 (2010)
  • Author(s): 堀本泰介, 山尾僚子, 前田健, 大川朝子, 岩附研子, 加藤健太郎, 明石博臣, 河岡義裕
  • Organizer: 第58回日本ウイルス学会
  • Place of Presentation: あわぎんホール(徳島)
  • Year and Date: 2010-11-08
• [Presentation] Vero 細胞における高増殖性インフルエンザワクチンシードウイルス開発のための基礎研究 (2009)
  • Author(s): 村上晋, 堀本泰介, 桂廣亮, 下島昌幸, 河岡義裕
  • Organizer: 第57回日本ウイルス学会
  • Place of Presentation: 都市センターホテル(東京)
  • Year and Date: 2009-11-26