A novel therapeutic strategy for zoonotic emerging and reemerging infections

• Project/Area Number: 17380179
• 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 The University of Tokyo, 医科学研究所, 准教授 (00222282)
• Co-Investigator(Kenkyū-buntansha): GOTOH Hideo 東京大学, 医科学研究所, 助教 (50323639) ; TAKADA Ayato 北海道大学, 人畜共通感染症リサーチセンター, 教授 (10292062) ; YASUDA Jiro 科学警察研究所, 法科学第一部, 室長 (10282518) ; SHIMOJIMA Masayuki 東京大学, 医科学研究所, 助教 (10422411)
• Co-Investigator(Renkei-kenkyūsha): TAKADA Ayato 北海道大学, 人畜共通感染症リサーチセンター, 教授 (10292062) ; YASUDA Jiro 科学警察研究所, 法科学第一部, 室長 (10282518) ; SHIMOJIMA Masayuki 東京大学, 医科学研究所, 助教 (10422411)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,780,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥2,280,000); Fiscal Year 2008: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2007: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2006: ¥3,800,000 (Direct Cost: ¥3,800,000); Fiscal Year 2005: ¥4,100,000 (Direct Cost: ¥4,100,000)
• Keywords: インフルエンザ / ワクチン / ベクター / 高病原性鳥インフルエンザ / H5N1

Research Abstract

人畜共通新興再興感染症は人類の脅威である。特に、H5N1 高病原性鳥インフルエンザの世界的な蔓延とヒトへの感染は、インフルエンザの新たな世界的大流行(パンデミック) を危惧させている。本研究では、こういった世界情勢を鑑み、H5N1 ワクチン開発のための基礎研究を実施した。その結果、不活化ワクチン製造のためのシードウイルスの発育鶏卵ならびにMDCK 細胞における増殖基盤を明らかにし、その知見をもとに高増殖性シードウイルスの作出に成功した。本成果は、今後のインフルエンザワクチン開発におおいに貢献することが期待される。

Research Products

• [Journal Article] Ko S-Y, Park S-H, Kweon M-N : Sublingual vaccination with influenza virus protects mice against lethal viral infection (2008)
  • Author(s): Song J-H, Lee A-Y, Nguyen HH, Czerkinsky C, Cubura N, Horimoto T
  • Journal Title: Proc Natl Acad Sci USA 105 Pages: 1644-1649
  • Peer Reviewed
• [Journal Article] Establishment of canine RNA polymerase I-driven reverse genetics for influenza A virus : its application for H5N1 vaccine production (2008)
  • Author(s): Murakami S, Horimoto T, Yamada S, Kakugawa S, Goto H, Kawaoka Y
  • Journal Title: J Virol 82 Pages: 1605-1609
  • Peer Reviewed
• [Journal Article] Growth determinants for H5N1 influenza vaccine seed viruses in MDCK cells (2008)
  • Author(s): Murakami S, Horimoto T, Le QM, Nidom CA, Chen H, Muramoto Y, Yamada S, Iwasa A, Iwatsuki-Horimoto K, Shimojima M, Iwata A, Kawaoka Y
  • Journal Title: J Virol 82 Pages: 10502-10509
  • Peer Reviewed
• [Journal Article] Cross-clade protective immunity of H5N1 influenza vaccines in a mouse model (2008)
  • Author(s): Murakami S, Iwasa A, Iwatsuki-HK, Ito M, Kiso M, Kida H, Takada A, Nidom CA, Le QM, Yamada S, Imai H, Sakai-T Y, Kawaoka Y, Horimoto T
  • Journal Title: Vaccine 26 Pages: 6398-6404
  • Peer Reviewed
• [Journal Article] Cross-clade protective immunity of H5N1 influenza vaccines in a mouse model. (2008)
  • Author(s): Murakami S
  • Journal Title: Vaccine 26 Pages: 6398-6404
  • Peer Reviewed
• [Journal Article] Growth determinants for H5N1 influenza vaccine seed viruses in MDCK cells. (2008)
  • Author(s): Murakami S
  • Journal Title: J Virol 82 Pages: 10502-10509
  • Peer Reviewed
• [Journal Article] Sublingual vaccination with influenza virus protects mice against lethal viral infection. (2008)
  • Author(s): Song J-H
  • Journal Title: Proc Natl Acad Sci USA 105 Pages: 1644-1649
  • Peer Reviewed
• [Journal Article] Enhanced growth of seed viruses for H5N1 influenza vaccines (2007)
  • Author(s): Horimoto T, Murakami S, Muramoto Y, Yamada S, Fujii K , Kiso M, Iwatsuki-H K, Kino Y, Kawaoka Y
  • Journal Title: Virology 366 Pages: 23-27
  • Peer Reviewed
• [Journal Article] A single intranasal immunization with inactivated influenza virus and alphagalactosylceramide induces long-term protective immunity without redirecting antigen to the central nervous system (2007)
  • Author(s): Youn H-J, Ko S-Y, Lee K-A, Ko H-J, Lee Y-S, Fujihashi K, Boyaka PN, Kim S-H, Horimoto T, Kweon M-N, Kang C-Y
  • Journal Title: Vaccine 25 Pages: 5189-5198
  • Peer Reviewed
• [Journal Article] An adenoviral vector-mediated reverse genetics system for influenza A virus generation (2007)
  • Author(s): Ozawa M, et. al.
  • Journal Title: J Virol 81 Pages: 9556-9559
  • Peer Reviewed
• [Journal Article] Enhanced growth of seed viruses for H5N1 influenza vaccines (2007)
  • Author(s): Horimoto T, et. al.
  • Journal Title: Virology 366 Pages: 23-27
  • Peer Reviewed
• [Journal Article] 新型インフルエンザワクチンの開発 (2007)
  • Author(s): 堀本 泰介
  • Journal Title: 治療学 41(10) Pages: 59-62
• [Journal Article] The development and characterization of H5 influenza virus vaccines derived from a 2003 human isolate (2006)
  • Author(s): Horimoto T, Takada A, Fujii K, Goto H, Hatta M, Watanabe S, Iwatsuki-H K, Ito M, Tagawa-S Y, Yamada S, Ito H, Ito T, Imai M, Itamura S, Odagiri T, Tashiro M, Lim W, Guan Y, Peiris M, Kawaoka Y
  • Journal Title: Vaccine 24 Pages: 3669-3676
  • Peer Reviewed
• [Journal Article] The cytoplasmic tail of the influenza A virus M2 protein plays a role in viral assembly (2006)
  • Author(s): Iwatsuki-H K, Horimoto T, Noda T, Kiso M, Maeda J, Watanabe S, Muramoto Y, Fujii K, Kawaoka Y
  • Journal Title: J Virol 80 Pages: 5233-5240
  • Peer Reviewed
• [Journal Article] Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors (2006)
  • Author(s): Yamada S, Suzuki Y, Suzuki T, Le MQ, Nidom CA, Sakai-Tagawa Y, Muramoto Y, Ito M, Kiso M, Horimoto T, Shinya K, Sawada M, Usui T, Murata T, Lin Y, Hay A, Haire LF, Stevens DJ, Russell RJ, Gamblin SJ, Skehel JJ, Kawaoka Y
  • Journal Title: Nature 444 Pages: 378-382
  • Peer Reviewed
• [Journal Article] The development and characterizationof H5 influenza virus vaccines derived from a 2003 human isolate. (2006)
  • Author(s): Horimoto T, et al.
  • Journal Title: Vaccine 24 Pages: 3669-3676
• [Journal Article] Hierarchy among viral RNA (vRNA) segments in their role in vRNA incorporation into influenza A virions. (2006)
  • Author(s): Muramoto Y, et al.
  • Journal Title: J Virol 80 Pages: 2318-2325
• [Journal Article] The cytoplasmic tail of the influenza A virus M2 protein plays a role in viral assembly. (2006)
  • Author(s): Iwatsuki-Horimoto K, et al.
  • Journal Title: J Virol 80 Pages: 5233-5240
• [Journal Article] Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptos. (2006)
  • Author(s): Yamada S, et al.
  • Journal Title: Nature 444 Pages: 378-382
• [Journal Article] Strategies for developing vaccines for H5N1 influenza A viruses. (2006)
  • Author(s): Horimoto T, et al.
  • Journal Title: Trends Mol Med 12 Pages: 506-514
• [Journal Article] 新型インフルエンザに対するワクチン開発 (2006)
  • Author(s): 堀本泰介
  • Journal Title: カレントテラピー 24 Pages: 54-58
• [Journal Article] Characterization of H5N1 influenza A viruses isolated during the outbreaks(in Japan) (2005)
  • Author(s): Mase M, Tsukamoto K, Imada T, Imai K, Tanimura N, Nakamura K, Yamamoto Y, Hitomi T, Kira T, Nakai T, Kiso M, Horimoto T, Kawaoka Y, Yamaguchi S
  • Journal Title: Virology 332 Pages: 167-176
  • Peer Reviewed
• [Journal Article] The importance of both the coding and segment-specific noncoding regions of the influenza A virus NS segment for its efficient incorporation into virions (2005)
  • Author(s): Fujii K, Fujii Y, Noda T, Muramoto Y, Watanabe T, Takada A, Goto H, Horimoto T, Kawaoka Y
  • Journal Title: Virol 79 Pages: 3766-3774
  • Peer Reviewed
• [Journal Article] Characterization of a human H5N1 influenza A virus isolated in 2003 (2005)
  • Author(s): Shinya K, Hatta M, Yamada S, Takada A, Watanabe S, Halfmann P, Horimoto T, Neumann G, Kim JH, Lim W, Guan Y, Peiris M, Kiso M, Suzuki T, Suzuki Y, Kawaoka Y
  • Journal Title: J Virol 79 Pages: 9926-9932
  • Peer Reviewed
• [Journal Article] Isolation of a genotypically unique H5N1 influenza virus from duck meat imported into Japan from China (2005)
  • Author(s): Mase M, Eto M, Tanimura N, Imai K, Tsukamoto K, Horimoto T, Kawaoka Y, Yamaguchi S
  • Journal Title: Virology 339 Pages: 101-109
  • Peer Reviewed
• [Journal Article] A drug-resistant H5N1 flu virus (2005)
  • Author(s): Le QM, Kiso M, Someya K, Sakai YT, Nguyen TH, Nguyen KH, Pham ND, Ngyen HH, Yamada S, Muramoto Y, Horimoto T, Takada A, Goto H, Suzuki T, Suzuki Y, Kawaoka Y
  • Journal Title: Nature 437 Pages: 1108-1108
  • Peer Reviewed
• [Journal Article] Characterization of H5N1 influenza A viruses isolated during the outbreaks in Japan. (2005)
  • Author(s): Mase, M
  • Journal Title: Virology 332 Pages: 167-176
• [Journal Article] Influenza : lessons from past pandemics, warnings from current incidents (2005)
  • Author(s): Horimoto, T
  • Journal Title: Nature Rev.Microbiol. 3 Pages: 591-600
• [Journal Article] パンデミックは再来する 鳥トリインフルエンザに隠された殺人鬼の影 (2005)
  • Author(s): 堀本泰介
  • Journal Title: 日経サイエンス 3月号 Pages: 30-35
• [Journal Article] A drug-resistant H5N1 flu virus. (2005)
  • Author(s): Le, Q.M
  • Journal Title: Nature 437(7062) Pages: 1108-1108
• [Journal Article] Characterization of a human H5N1 influenza A virus isolated in 2003. (2005)
  • Author(s): Shinya, K
  • Journal Title: J.Virol. 79 Pages: 9926-9932
• [Journal Article] 鳥インフルエンザウイルス (2005)
  • Author(s): 堀本泰介
  • Journal Title: メディカルサイエンスダイジェスト 31(1) Pages: 9-12
• [Journal Article] A protective immune response in mice to viral components other than hemagglutinin in a live influenza A virus vaccine model (2004)
  • Author(s): Horimoto T, Takada A, Iwatsuki-H K, Kawaoka Y
  • Journal Title: Vaccine 22 Pages: 2244-2247
  • Peer Reviewed
• [Journal Article] Influenza A viruses possessing type B hemagglutinin and neuraminidase : potential as vaccine components (2004)
  • Author(s): Horimoto T, Iwatsuki-H K, Hatta M, Kawaoka Y
  • Journal Title: Microb Infect 6 Pages: 579-583
  • Peer Reviewed
• [Journal Article] Generation of influenza A virus NS2 (NEP) mutants with an altered nuclear export signal sequence (2004)
  • Author(s): Iwatsuki-H K, Horimoto T, Fujii Y, Kawaoka Y
  • Journal Title: J Virol 78 Pages: 10149-10155
  • Peer Reviewed
• [Presentation] H5N1不活化インフルエンザワクチンのクレード間交差防御免疫能の解析 (2008)
  • Author(s): 村上晋, 岩佐彩香, 岩附研子, 伊藤睦美, 木曽真紀, 喜田宏, 高田礼人, CA Nidom, Le Quynh Mai, 山田晋弥, 今井博貴, 坂井(田川)優子, 河岡義裕, 堀本泰介
  • Organizer: 第56回日本ウイルス学会
  • Place of Presentation: 岡山
• [Presentation] Growth determinants for H5N1 influenza vaccine seed viruses in MDCK cells. XIV. International Congress of Virology (2008)
  • Author(s): Murakami S, Horimoto T, Muramoto Y, Yamada S, Iwasa A, Iwatsuki-H K, Shimojima M, Kawaoka Y
  • Organizer: 国際ウイルス学会
  • Place of Presentation: イスタンブール
• [Presentation] Growth determinants for H5N1 influenza vaccine seed viruses in MDCK cells. (2008)
  • Author(s): Murakami S
  • Organizer: XIV. International Congress of Virology
  • Place of Presentation: Istanbul
• [Presentation] アデノウイルスベクターを用いたA型インフルエンザウイルスのリバースジェネティクス法 (2007)
  • Author(s): 小澤 真, ら
  • Organizer: 第55回日本ウイルス学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-10-22
• [Presentation] イヌRNAポリメラーゼIプロモーターを用いたインフルエンザウイルスリバースジェネティクス系の確立とH5N1ワクチンシードウイルスの作製 (2007)
  • Author(s): 村上晋, 堀本泰介, 河岡義裕
  • Organizer: 第55回日本ウイルス学会
  • Place of Presentation: 札幌
• [Presentation] H5N1ワクチンシードウイルスのMDCK 細胞での増殖性を決める因子 (2007)
  • Author(s): 村上晋, 堀本泰介, 村本裕紀子, 岩佐彩香, 山田晋弥, 岩附研子, 岩田晃, 河岡義裕
  • Organizer: 第55回日本ウイルス学会
  • Place of Presentation: 札幌
• [Presentation] インフルエンザ不活化ワクチンの製造基材である発育鶏卵でよく増殖するH5N1ワクチンシードウイルス候補株の作出 (2005)
  • Author(s): 堀本泰介, 本裕紀子, 藤井健, 山田晋弥, 岩附研子, 城野洋一郎, 河岡義裕
  • Organizer: 第53回日本ウイルス学会
  • Place of Presentation: 横浜
• [Book] ウイルスと感染のメカニズム : インフルエンザウイルス 微生物感染学(光山正雄) (2005)
  • Author(s): 堀本泰介, 河岡義裕
  • Publisher: 南山堂
• [Book] 微生物感染学 (2005)
  • Author(s): 堀本泰介
  • Total Pages: 312
  • Publisher: 南山堂
• [Patent(Industrial Property Rights)] New composition comprising influenza virus vectors, useful in preparing high titer influenza viruses for use immunizing an individual against a pathogen (2007)
  • Inventor(s): KAWAOKA Y, HORIMOTO T, MURAKAMI S
  • Industrial Property Rights Holder: KAWAOKA Y, HORIMOTO T, MURAKAMI S
  • Acquisition Date: 2007-10-04
  • Overseas