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Development of a vaccine against enterohemorrhagic Escherichia coli

Research Project

Project/Area Number 10357003
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Bacteriology (including Mycology)
Research InstitutionNational Institute of Infections Diseases (1999-2000)
Research Institute, International Medical Center of Japan (1998)

Principal Investigator

TAKEDA Yoshifumi  National Institute of Infections Diseases, Director - General, 所長 (30029772)

Co-Investigator(Kenkyū-buntansha) YAMASAKI Shinji  Research Institute, International Medical Center of Japan, Division Director, 適正技術開発・移転研究部, 室長 (70221653)
HAMABATA Takashi  Research Institute, International Medical Center of Japan, Division Director, 感染・熱帯病研究部, 室長 (40311427)
MAKINO Sou-ichi  Department of Veterinary Microbiology, University of Agriculture and Veterinary Medicine, Associate Professor, 畜産学部, 助教授 (30181621)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥32,500,000 (Direct Cost: ¥32,500,000)
Fiscal Year 2000: ¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 1999: ¥9,500,000 (Direct Cost: ¥9,500,000)
Fiscal Year 1998: ¥14,000,000 (Direct Cost: ¥14,000,000)
KeywordsEnterohemorrhagic Escherichia coli / Non-toxic mutant / Vaccine strain / Porcine edema disease / VT2vp1 / Protective efficacy / Vero toxin / Stx2 / 生菌ワクチン / VT2 / 幼弱ウサギ / 幼弱ブタ / 無毒変異毒素 / 無毒変異要素
Research Abstract

Enterohemorrhagic Escherichia coli(EHEC) is isolated from not only humans but also from cattle. EHEC infection in cattle such as cows and pigs is a big prolem and EHEC contaminated in feces of human infection. Thus a development of a vaccine strain against EHEC infection in cattle may prevent the occurrence of EHEC infection in human, and therefore prevent a complication such as hemolytic uremic syndrome.
In this study we developed a vaccine strain of EHEC that causes porcine edema disease. Effectiveness of the developed vaccine strain was also demonstrated. A mutant strain constructer retained immunogenicity but lost Vero cell cytotoxicy, and produced genetically modified toxin by replaciy glutamate with glutamine at position 167 and ayine with leucine at position 170 of the A subunit of Vero toxin (Stx2e). As the parent wild strain was pathogenic to pigs but the mutant strain was not, the mutant strain named as YT106 was given to the pigs to examine its protective immunity against edema disease. All 20 pigs vaccinated with TY106 survived but only 8 of 20 nonvaccinated pigs survived after the challenge with a wild strain. Also, the 8 survived pigs had decreased rates of gain relative to those of the controls. Blood IgG and intestinal IgA titers increased 3.3 and 1.6 times, respectively, more then the control, showing that YT106 might be a good candidate of a live-attenuated vaccine strain to protect against edema disease.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (24 results)

All 2001 2000 1999 1998 Other

All Journal Article (9 results) Publications (15 results)

  • [Journal Article] Protective effect of Lactobacillus strain Shirota on Shiga toxin-producing Escherchia coli O157:H7 infection in infant rabbits.2001

    • Author(s)
      Y.Takeda
    • Journal Title

      Infect.Immun. 69

      Pages: 1101-1108

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Protective effect of Lactobacillus strain Shirota on Shiga toxin-producing Escherchia toll O157:H7 infection in infant rabbits.2001

    • Author(s)
      Y.Takeda
    • Journal Title

      Infect.Immun. 69

      Pages: 1101-1108

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Shiga toxin activates p38 MAP kinase through cellular Ca^<2+> increase in Vero cells.2000

    • Author(s)
      Y.Takeda
    • Journal Title

      FEBS Lett. 485

      Pages: 94-98

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Analysis of the genes responsible for the O-antigen synthesis in enterohemorrhagic Escherichia coli 157.1999

    • Author(s)
      Y.Takeda
    • Journal Title

      Microb.Pathog. 26

      Pages: 235-247

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Identification and characterization of a newly isolated Shiga toxin 2-converting phage from Shiga toxin-producing Escherichia coli.1998

    • Author(s)
      Y.Takeda
    • Journal Title

      Infect.Immun. 66

      Pages: 4100-4107

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Inhibition of in vitro groth of Shiga toxin-producing Escherichia coli O157:H7 by probiotic Lactobacillus strains due to production of lactic acid.

    • Author(s)
      Y.Takeda
    • Journal Title

      Int.J.Food Microbial. in perss

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Genetically modified Shiga toxin 2e (Stx2e) producing Escherichia cili is a vaccine candidate for porcine edema.

    • Author(s)
      Y.Takeda
    • Journal Title

      Microb.Pathog. in perss

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Inhibition of in vitro groth of Shiga toxin-producing Escherichia coli O157:H7 by probiotic Lactobacillus strains due to production of lactic acid.

    • Author(s)
      Y.Takeda
    • Journal Title

      Int.J.Food Microbiol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Journal Article] Genetically modified Shiga toxin 2e (Stx2e) producing Escherichia cili is a vaccine candidate for porcine edema.

    • Author(s)
      Y.Takeda
    • Journal Title

      Microb.Pathog. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Takeda: "Identification and characterization of a newly isolated Shiga toxin 2-converting phage from Shiga toxin-producing Escherichia coli."Infect.Immun.. 66. 4100-4107 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Takeda: "Analysis of the genes responsible for the O-antigen synthesis in enterohemorragic Escherichia coli 157.."Microb.Pathog.. 26. 235-247 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Takeda: "Shiga toxin activates p38 MAP kinase through cellular Ca^<2+> increase in Vero cells."FEBS Lett.. 485. 94-98 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Takeda: "Protective effect of Lactobacillus strain Shirota on Shiga toxin-producing Escherchia coli O157:H7 infection in infant rabbits."Infect.Immun.. 69. 1101-1108 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Takeda: "Inhibition of in vitro groth of Shiga toxin-producing Escherichia coli O157:H7 by probiotic Lactobacillus strains due to production of lactic acid."Int.J.Food Microbial.. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Takeda: "Genetically Modified Shiga Toxin 2e (Stx2e) Producing Escherichia cili is a Vaccine Candidate for Porcine Edema."Microb.Pathog.. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Shimizu et al.: "Analysis of the genes responsible for the O.antiger synthesis in enterohemorrhagic Eschrichia coli O157"Microb.Pathog.. 26. 235-247 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] C.Yamasaki,Y.Natori,X-T.Zeng,M.Ohmura,S.Yamasaki,Y.Takeda and Y.Natori: "Induction of cytokines in a human colon epithelial cell line by Shiga toxin 1(Stx 1)and Stx 2 but not by non-toxic mutant Stx 1 which lacks N-glycosidase activity"FEBS Letters. 442. 231-234 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Hoshino,O.Takeuchi,T.Kawai,H.Sanjo,Y.Ogawa,Y.Takeda,K.Takeda and S.Akira: "Toll-like receptor 4(TLR4)-deficient mice hyporesponsive to lipopolysaccharide : evidence for TLR4 as the Lps gene product"Immunol. 162. 3749-3752 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Hoshino,H.Tsutsui,T.Kawai,K.Takeda,K.Nakanishi,Y.Taked and S.Akira: "Generation of IL-18 receptor-deficient mice : evidence for IL-1 receptor-related protein as an essential IL-18 binding receptor"J.Immunol. 162. 5041-5044 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Yamamoto,H.Kiyono,S.Yamamoto,E.Batanero M-N.Kweon,S.Otake,M.Azuma,Y.Takeda and J.R.McGhee: "Direct effects on antigen-presenting cells and T lymphocytes explain the adjuvanticity of a nontoxic cholera toxin mutant"J.Immunol. 162. 7015-7021 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] A.Basu,A.K.Mukhopadhyay,P.Garg,S.Chakraborty,T.Ramamurthy,S.Yamasaki,Y.Takeda and G.B.Nair: "Diversity in the arrangement of the CTX prophages in classical strains of Vibric cholerae O1"FEMS Microb.Letters. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Shimizu et al.: "Analysis of the genes responsible for the O-autige synthesis in enterohemorrhegic Esseecichia coli O157" Miwob.palhog.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] C.Yamasaki: "Induction of cytokines in a human colon epitherial cell line by Shesa toxin 1(Stx1)and Stx2・・・" FEBS Letters. 442. 231-234 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Watarai et al: "Iaentification and Charactenigation of a neney isolatan Sliga toxin 2-convertive of phase." Infection and Immunity. 66. 4100-4107 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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