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Isolation of humonal monoclonal antibody cross-reactively neutralizing against shiga toxin type 1 and 2 and treating a patient suffering HUS

Research Project

Project/Area Number 24590539
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionFujita Health University

Principal Investigator

TSUJI Takao  藤田保健衛生大学, 医学部, 教授 (60171998)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords腸管出血性大腸菌 / 致死毒素(Stx1と2) / 経鼻投与ワクチン / ヒトモノクローナル抗体 / HUS治療薬 / 腸管出血性大腸菌(EHEC) / HUS / Stx1と2 / 抗体治療薬 / Stx2B-His / ニワトリIgY
Outline of Final Research Achievements

Enterohemorrhagic Escherichia coli (EHEC) produces Stx1 and Stx2 causing severe diseases like hemolytic uremic syndrome (HUS). As there is no vaccine or no curative for these diseases caused by both toxins, we have been trying to isolate monoclonal antibody or polyclonal antibodies cross-reactively neutralizing both toxins. We already reported that nasal subunit-vaccine such as Stx2B-His with a mutant heat-labile enterotoxin induced polyclonal antibodies cross-reactively neutralizing both toxins (Vaccine,24:3591,2006、26:469,2008、26:2092.2008).Then, in this project, we try to isolate a monoclonal antibody, which will neutralize both toxins cross-reactively and use for the treatment of severe diseases like HUS caused by both toxins.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (23 results)

All 2015 2014 2013 2012

All Journal Article (10 results) (of which Peer Reviewed: 9 results) Presentation (12 results) Book (1 results)

  • [Journal Article] Isolation of B subunit-specific monoclonal antibody clones that strongly neutralize the toxicity of Shiga toxin 2.2015

    • Author(s)
      Arimitsu H, Sasaki K, Iba, Y; Kurosawa, Y; Shimizu, T; Tsuji, T.
    • Journal Title

      Microbiol Immunol..

      Volume: 59 Pages: 71-81

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of Shiga toxin 2e-specific chicken egg yolk immunoglobulin: production and neutralization activity.2014

    • Author(s)
      Arimitsu H, Sasaki K, Kohda T, Shimizu T, Tsuji T.
    • Journal Title

      Microbiol Immunol.

      Volume: 58 Pages: 643-648

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Whole genomic analysis of human G12P[6] and G12P[8] rotavirus strains that have emerged in Kenya: Identification of porcine-like NSP4 genes.2014

    • Author(s)
      Komoto S, Wandera Apondi E, Shah M, Odoyo E, Nyangao J, Tomita M, Wakuda M, Maeno Y, Shirato H, Tsuji T, Ichinose Y, Taniguchi K.
    • Journal Title

      Infect Genet Evol.

      Volume: 27 Pages: 277-293

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Large-scale preparation of Shiga toxin 2 in Escherichia coli for toxoid vaccine antigen production.2013

    • Author(s)
      Arimitsu H, Sasaki K, Shimizu T, Tsukamoto K, Shimizu T and Tsuji T
    • Journal Title

      Microbiol Immunol.

      Volume: 57(1) Pages: 38-45

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Simple Method for Shiga Toxin 2e Purification by Affinity Chromatography via Binding to the Divinyl Sulfone Group.2013

    • Author(s)
      Arimitsu H, Sasaki K, Kojima H, Yanaka T, Tsuji T.
    • Journal Title

      PLoS One.

      Volume: 8(12) Pages: 83577-83577

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recombinant Shiga toxin B subunit can induce neutralizing IgY antibody2012

    • Author(s)
      Neri P, Tokoro S, Sugiyama T, Umeda K, Shimizu T, Tsuji T, Kodama Y, Mori H
    • Journal Title

      Biol. Pharm. Bull

      Volume: 35 Pages: 917-923

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Randomized placebo-controlled clinical trial of immunoglobulin Y as adjunct to standard supportive therapy for rotavirus-associated diarrhea among pediatric patients2012

    • Author(s)
      Rahman S, Higo-Moriguchi K, Htun KW, Taniguchi K, Icatlo FC Jr, Tsuji T, Kodama Y, Van Nguyen S, Umeda K, Oo HN, Myint YY, Htut T, Myint SS, Thura K, Thu HM, Fatmawati NN, Oguma K
    • Journal Title

      Vaccine.

      Volume: 30

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Correlation Coefficient between various Fac.related with the oral environment in technical high School Students2012

    • Author(s)
      Kim SY, Honda S, Tsuji T, BangSH
    • Journal Title

      Internal J Clinical preventive Dentistry

      Volume: 8 Pages: 7-14

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] P19 embryonal carcinoma cells exhibit high sensitivity to botulinum type C and D/C mosaic neurotoxins2012

    • Author(s)
      Tsukamoto K, Arimitsu H, Ochi S, Nakamura K, Tanaka Y, Nuemket N, Taniguchi K, Kozaki S, Tsuji T.
    • Journal Title

      Microbiol Immunol.

      Volume: 56 Pages: 664-672

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Staphylococcal enterotoxin A has potent superantigenic and emetic activities but not diarrheagenic activity2012

    • Author(s)
      Maina EK, Hu DL, Tsuji T, Omoe K, Nakane A.
    • Journal Title

      Int J Med Microbiol

      Volume: 302 Pages: 88-95

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] ボツリヌスC型毒素の神経細胞への取り込みと細胞内局在.2015

    • Author(s)
      塚本健太郎, 尾関千賀子, 幸田知子, 辻孝雄
    • Organizer
      第88回日本細菌学会総会
    • Place of Presentation
      岐阜市、長良川国際会議場
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 毒性を中和する抗Shiga toxin 2モノクローナル抗体の作製2015

    • Author(s)
      有満秀幸, 佐々木慶子, 辻孝雄
    • Organizer
      第88回日本細菌学会総会
    • Place of Presentation
      岐阜市、長良川国際会議場
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Shiga toxin2を中和するモノクローナル抗体の作製及び性状解析.2014

    • Author(s)
      有満秀幸, 佐々木慶子, 辻孝雄.
    • Organizer
      第51回日本細菌学会中部支部総会
    • Place of Presentation
      金沢市、北陸大学薬学部アネックス・フォーム
    • Year and Date
      2014-10-17 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] ゲノム編集技術によるボツリヌスC型神経毒素低感受性細胞の作製2014

    • Author(s)
      塚本健太郎, 尾関千賀子, 幸田知子, 辻孝雄.
    • Organizer
      第51回日本細菌学会中部支部総会
    • Place of Presentation
      金沢市、北陸大学薬学部アネックス・フォーム
    • Year and Date
      2014-10-17 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] ボツリヌスC型神経毒素の細胞内動態の可視化と細胞内侵入機構について2014

    • Author(s)
      塚本健太郎, 尾関千賀子, 幸田知子, 辻 孝雄
    • Organizer
      第61回トキシンシンポジウム
    • Place of Presentation
      徳島県鳴門市、ルネッサンスリゾートナルト
    • Year and Date
      2014-09-03 – 2014-09-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] 志賀毒素バリアントStx2eのアフィニティ精製法の確立.2013

    • Author(s)
      有満秀幸, 佐々木慶子, 児島広枝, 谷中匡, 塚本健太郎, 辻孝雄.
    • Organizer
      第60回毒素シンポジウム
    • Place of Presentation
      兵庫県宍粟市
    • Related Report
      2013 Research-status Report
  • [Presentation] 志賀毒素バリアントStx2eの簡易精製法.2013

    • Author(s)
      有満秀幸, 佐々木慶子, 児島広枝, 谷中匡, 塚本健太郎, 越智定幸, 辻孝雄.
    • Organizer
      第156回日本獣医学会
    • Place of Presentation
      岐阜市
    • Related Report
      2013 Research-status Report
  • [Presentation] ジビニルスルホンとの相互作用による志賀毒素バリアントStx2eの精製法.2013

    • Author(s)
      有満秀幸, 佐々木慶子, 辻孝雄.
    • Organizer
      第50回日本細菌学会中部支部総会
    • Place of Presentation
      愛知県蒲郡市
    • Related Report
      2013 Research-status Report
  • [Presentation] ボツリヌスC型神経毒素重鎖C末端領域の細胞侵入過程の解析.2013

    • Author(s)
      塚本健太郎, 尾関千賀子, 辻孝雄.
    • Organizer
      第50回日本細菌学会中部支部総会
    • Place of Presentation
      愛知県蒲郡市
    • Related Report
      2013 Research-status Report
  • [Presentation] ジビニルスルホン基を介した志賀毒素バリアントStx2eのアフィニティ精製法2013

    • Author(s)
      有満秀幸、佐々木慶子、辻孝雄
    • Organizer
      第87回日本細菌学会総会
    • Place of Presentation
      ;東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 胚性腫瘍細胞P19を用いたボツリヌス神経毒素の作用機構の解析2013

    • Author(s)
      塚本健太郎、有満秀幸、越智定幸、中村佳司、幸田知子、小崎俊司、辻孝雄
    • Organizer
      第85回日本細菌学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 神経分化したP19細胞に対するボツリヌス神経毒素の感受性について2012

    • Author(s)
      塚本健太郎、有満秀幸、越智定幸、中村佳司、幸田知子、小崎俊司、辻孝雄
    • Organizer
      第59回トキシンシンポジウム
    • Place of Presentation
      北海道
    • Related Report
      2012 Research-status Report
  • [Book] 細菌の病原因子2012

    • Author(s)
      辻 孝雄
    • Publisher
      医学書院
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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