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Amyloid beta-42-mimotope displaying M13 bacteriophage for vaccine vehicle of Alzheimer's disease

Research Project

Project/Area Number 21310144
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Living organism molecular science
Research InstitutionKagoshima University

Principal Investigator

SUGIMURA Kazuhisa  鹿児島大学, 理工学研究科, 教授 (80127240)

Co-Investigator(Kenkyū-buntansha) HASHIGUCHI Syuhei  鹿児島大学, 理工学研究科, 助教 (40295275)
伊東 祐二  鹿児島大学, 理工学研究科(工学系), 准教授 (60223195)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2011: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2010: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2009: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Keywordsアルツハイマー認知症 / M13ファージ / ワクチン / 自然免疫 / ミミックペプチド / アミロイドベーター / MyD88 / TLR9 / ヒト抗体 / Aβ42 / 受動免疫 / ファージライブラリ / J20 / オリゴマー
Research Abstract

Bacteriophage evokes strong antibody production by means of innate immunity. Recently, we have established B6 mimotope peptide(B6-C15) which mimics the structure of amyloid・42(A・) fibril using human single-chain Fv(B6) specific to A・42 fibril. This mimotope peptide binds to A・42 oligomers and inhibits formation of A・42 fibril in vitro. We investigated whether M13 bacteriophage displaying B6-mimotope peptide(B6-C15-phage) could produce A・42 fibril specific antibody response in mice. When mice were immunized i. p. with B6-C15-phage in PBS solution, they produced anti-A・42 fibril specific IgG response in two weeks. This finding suggested a promising vaccination strategy for immunotherapy of Alzheimer's disease without the involvement of A・42-specific T cell immunity(BBRC 402 : 19-22, 2010, and J. Neuroimmunol. 236 : 27-38, 2011).

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (26 results)

All 2012 2011 2010 2009 2008

All Journal Article (8 results) (of which Peer Reviewed: 7 results) Presentation (15 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 2 results)

  • [Journal Article] Direct evidence of generation and accumulation ofβ-sheet-rich prion protein in scrapie-infected neuroblastoma cells with a human IgG1 antibody specific for the b-form prion protein2012

    • Author(s)
      Toshiya Kubota, Yuta Hamazoe, Shuhei Hashiguchi, Daisuke Ishibashi, Kazuyuki Akasaka, Noriyuki Nishida, Shigeru Katamine, Suehiro Sakaguchi, Ryota Kuroki, Toshihiro Nakashima, and Kazuhisa Sugimura
    • Journal Title

      J. Biol. Chem

      Volume: 287 Pages: 14023-14039

    • URL

      http://www.jbc.org/content/287/17/14023.full

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Direct evidence of generation and accumulation of β-sheet-rich prion protein in scrapie-infected neuroblastoma cells with a human IgG1 antibody specific for the b-form prion protein2012

    • Author(s)
      Toshiya Kubota, Yuta Hamazoe, Shuhei Hashiguchi, Daisuke Ishibashi, Kazuyuki Akasaka, Noriyuki Nishida, Shigeru Katamine, Suehiro Sakaguchi, Ryota Kuroki, Toshihiro Nakashima, Kazuhisa Sugimura
    • Journal Title

      J.Biol.Chem.

      Volume: 287 Pages: 14023-14039

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A mimotope peptide of Aβ42 fibril-specific antibodies with Aβ42 fibrillation inhibitory activity induces anti-Aβ42 conformer antibody response by a displayed form on an M13 phage in mice2011

    • Author(s)
      Koichi Tanaka, Masaaki Nishimura, Yuya Yamaguchi, Shuhei Hashiguchi, Sho Takiguchi, Makoto Yamaguchi, Haruna Tahara, Takuma Gotanda, Risa Abe, Yuji Ito, Kazuhisa Sugimura
    • Journal Title

      J. Neuroimmunology

      Volume: 236 Pages: 27-38

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/21641049

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A mimotope peptide of Aβ42 fibril-specific antibodies with Aβ42 fibrillation inhibitory activity induces anti-Aβ42 conformer antibody response by a displayed form on an M13 phage in mice2011

    • Author(s)
      Koichi Tanaka, Masaaki Nishimura, Yuya Yamaguchi, Shuhei Hashiguchi, Sho Takiguchi, Makoto Yamaguchi, Haruna Tahara, Takuma Gotanda, Risa Abe, Yuji Ito, Kazuhisa Sugimura
    • Journal Title

      J.Neuroimmunology

      Volume: 236 Pages: 27-38

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ファージディスプレイとBeyond antibody :~抗体様分子による分子標的~2010

    • Author(s)
      橋口周平、伊東祐二、田中孝一、松木園美穂、村岡賢、杉村和久
    • Journal Title

      生化学

      Volume: 82 Pages: 710-726

    • NAID

      10027502225

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Immunological basis of M13 phage vaccine : Regulation under MyD88 and TLR9 signaling.2010

    • Author(s)
      Shuhei Hashiguchi, Yuya Yamaguchi, Osamu Takeuchi, Shizuo Akira, Kazuhisa Sugimura
    • Journal Title

      BBRC

      Volume: 402 Pages: 19-22

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of Human Single-Chain Antibodies Against Highly Pathogenic Avian Influenza H5N1 Viruses : Mimotope and Neutralizing Activity.2010

    • Author(s)
      JiuPian Yang, Reiko Yoshida, Yuji Ito, Yuki Kariya, Xu Zhang, Shuhei Hashiguchi, Toshihiro Nakashima, Yasuo Suda, Ayato Takada, Kazuhisa Sugimura.
    • Journal Title

      J.Biochem.

      Volume: 148 Pages: 504-515

    • NAID

      10027879101

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Contribution of IL-18 to eosinophilic airway inflammation induced by immunization and challenge with Staphyloccus aureus proteins.2010

    • Author(s)
      May Kuroda-Morimoto, Hidehisa Tanaka, Nobuki Hayashi, Masakiyo Nakahira, Tasutomo Imai, Michiko Imamura, Koubun Yasuda, Shizue Yumikura-Futatsugi, Kiyoshi Matsui, Toshihiro Nakashima, Kazuhisa Sugimura, Hiroko Tsutsui, Hajime Sano, Keiji Nakanishi
    • Journal Title

      Int.Immunol.

      Volume: 22 Pages: 561-570

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Amyloid Beta-42-Mimotope Displaying M13 Bacteriophage for Vaccine Vehicle of Arzheimer's Disease2011

    • Author(s)
      Kazuhisa Sugimura, Shuhei Hashiguchi, Teppei Osako, Sotaro Kawabata, Risa Abe, Shiro Nakagawa
    • Organizer
      5th Vaccine and ISV Annual Global Congress
    • Place of Presentation
      Seattle
    • Year and Date
      2011-10-04
    • Related Report
      2011 Final Research Report
  • [Presentation] Amyloid beta-42-mimotope displaying M13 bacteriophage for Vaccine vehicle of Alzheimer's disease2011

    • Author(s)
      Kazuhisa Sugimura, Shuhei Hashiguchi, Teppei Osako, Sotaro Kawabata, Risa Abe, Shiro Nakagawa
    • Organizer
      5th Vaccine and ISV Annual Global Congress
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2011-10-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] アルツハイマー病モデルマウス(J20)脳内での、繊維状アミロイドβ(Aβ)に特異的な抗体(B7)によるAβプラークの免疫組織学的解析2011

    • Author(s)
      川畑壮大朗、安部梨沙、田中孝一、大迫哲平、橋口周平、鈴木賢太朗、山田源、中島敏博、中河史朗、杉村和久
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2011-09-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] M13 bacteriophage for vaccine vehicle of Alzheimer's disease2011

    • Author(s)
      Kazuhisa Sugimura, Shuhei Hashiguchi, Teppei Osako, Sotaro Kawabata, Risa Abe
    • Organizer
      1st Oxford International Bacteriophage Conference, Phage 2011
    • Place of Presentation
      St Hilda's college Oxford University
    • Year and Date
      2011-09-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] Amyloid beta 42-mimotope-displaying M13 phage induce anti-amyloid beta 42 antibody without adjuvant2011

    • Author(s)
      Kazuhisa Sugimura, Risa Abe, Sotaro Kawabata, Teppei Osako, Takuma Gotanda, Shuhei Hashiguchi, Shiro Nakagawa
    • Organizer
      Alzheimer's Association International Conference on Alzheimer's Disease 2011
    • Place of Presentation
      Paris, France
    • Year and Date
      2011-07-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] Amyloid beta42-mimotope-displaying M13 phage induce anti-amyloid beta42antibody without adjuvant2011

    • Author(s)
      大迫哲平、安部梨沙、川畑壮大朗、田中孝一、五反田卓摩、橋口周平、中河志朗、杉村和久
    • Organizer
      第40回日本免疫学会学術集会記録
    • Place of Presentation
      千葉,幕張メッセ
    • Related Report
      2011 Final Research Report
  • [Presentation] Strong innate immunity to M13 bacteriophage : Implication for vaccine development2011

    • Author(s)
      Shuhei Hashiguchi, Takuma Gotanda, Yuta Hamazoe, Kazuhisa Sugimura
    • Organizer
      第40回日本免疫学会学術集会記録
    • Place of Presentation
      千葉,幕張メッセ
    • Related Report
      2011 Final Research Report
  • [Presentation] Strong Innate Immunity to M13 Bacteriophage : Implication for Vaccine Development2011

    • Author(s)
      Shuhei Hashiguchi, Takuma Gotanda, Yuta Hamazoe, Tsuyoshi Tsurumaru, Kazuhisa Sugimura
    • Organizer
      5th Vaccine and ISV Annual Global Congress
    • Place of Presentation
      Seattle, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] アルツハイマー病モデルマウス(J20)脳内での、線維状アミロイドβ(Aβ)に特異的な抗体(B7)によるAβプラークの免疫組織学的解析2011

    • Author(s)
      川畑壮大朗、安部梨沙、田中孝一、大迫哲平、橋口周平、鈴木賢太郎、山田源、中島敏博、中河志朗、杉村和久
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      兵庫,神戸ポートアイランド
    • Related Report
      2011 Final Research Report
  • [Presentation] M13バクテリオファージ免疫におけるTLRファミリー分子の役割について2010

    • Author(s)
      田原春菜、橋口周平、山口雄也、竹内理、審良静男、杉村和久
    • Organizer
      BMB2010第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸市
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] Immunological basis of M13 phage vaccines : an effective vaccine design tested in a mouse model of Alzheimer's disease.2010

    • Author(s)
      Hashiguchi S, Yamaguchi Y, Tahara H, Yamada T, Kai S, Abe R, Tanaka K, Sugimura K.
    • Organizer
      5th International Peptide Symposium
    • Place of Presentation
      京都市
    • Year and Date
      2010-12-06
    • Related Report
      2010 Annual Research Report
  • [Presentation] Essential role of MyD88 in humoral response to M13 bacteriophage in mice and negative role of TLR9 in IgG1 response.2010

    • Author(s)
      Hashiguchi S, Yamaguchi Y, Takeuchi O, Akira S, Sugimura K.
    • Organizer
      14th International Congress of Immunology
    • Place of Presentation
      神戸市
    • Year and Date
      2010-08-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] Amyloid beta42-mimotope-displaying M13 phage induce anti-amyloid beta42antibody without adjuvant2010

    • Author(s)
      Kazuhisa Sugimura, Risa Abe, Sotaro Kawabata, Teppei Osako, Takuma Gotanda, Shuhei Hashiguchi, Shiro Nakagawa
    • Organizer
      Alzheimer's Association International Conference on Alzheimer's Disease
    • Place of Presentation
      Paris, France
    • Related Report
      2011 Final Research Report
  • [Presentation] Immunological basis of phage vaccine as an experimental model using Alzheimer's disease model mice, J20 immunized with a mimotope-phage clone selected by a fibrillar Abeta42-specific antibody.2010

    • Author(s)
      Yuya Yamaguchi, Shuhei Hashiguchi, Koichi Tanaka, Risa Abe, Kazuhisa Sugimura.
    • Organizer
      The Immunotherapeutics and vaccine summit
    • Place of Presentation
      Cambridge, MA
    • Related Report
      2010 Annual Research Report
  • [Presentation] アミロイドベータ1-42ミモトープをディスプレイしたM13ファージが誘導する免疫応答の解析2009

    • Author(s)
      山口雄也, 橋口周平, 永尾宏子, 山田昴, 杉村和久
    • Organizer
      第39回日本免疫学会総会・学術集会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Year and Date
      2009-12-03
    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] アミロイドBペプチドのミミック分子を用いたペプチドワクチン2010

    • Inventor(s)
      杉村和久
    • Industrial Property Rights Holder
      鹿児島大学
    • Industrial Property Number
      2009-538294
    • Filing Date
      2010-03-15
    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] アミロイドβ線維化阻害ペプチド2008

    • Inventor(s)
      杉村和久
    • Industrial Property Rights Holder
      鹿児島大学
    • Filing Date
      2008-10-22
    • Related Report
      2011 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] アミロイドβペプチドのミミック分子を用いたペプチドワクチン2008

    • Inventor(s)
      杉村和久
    • Industrial Property Rights Holder
      鹿児島大学
    • Filing Date
      2008-10-22
    • Related Report
      2011 Final Research Report
    • Overseas

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Published: 2009-04-01   Modified: 2016-04-21  

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