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Development of the passive immunization for prevention of dental caries using B cell epitopes of PAc.

Research Project

Project/Area Number 03557079
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionNational Institute of Health

Principal Investigator

OKAHASHI Nobuo  NIH, Oral Science, Chief Researcher, 口腔科学部, 主任研究官 (40150180)

Co-Investigator(Kenkyū-buntansha) SENPUKI Hidenobu  NIH, Oral Science, Researcher, 口腔科学部, 研究員 (20250186)
NISIZAWA Tosiki  NIH, Oral Science, Chief Researcher, 口腔科学部, 主任研究官 (00072942)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1992: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥4,500,000 (Direct Cost: ¥4,500,000)
KeywordsPassive immunization / T cell epitope / B cell epitope / Dental caries / Peptide antigen / PAc / Streptococcus mutans / う蝕予防 / ミュータンスレンサ球菌 / ワクチン / タンパク質抗原 / ミュ-タンスレンサ球菌
Research Abstract

A fimbria like surface protein (PAc) of Streptococcus mutans with a molecular mass of 190 kDa is one of the strong surface antigens of the Streptococcus and is involved in the initial attachment of this microorganism to the tooth surface. Thus, the protein antigen has been considered to be a good candidate for an anti-caries vaccine. Actually, it was successfully used as vaccine in the animal experiments. Passive immunization with monoclonal antibodies against the PAc was also reported to prevent dental caries in monkeys.
In the present project, we constructed 7 truncated PAc fragments by using a DNA engineering and suggested that the alanine-rich repeating region (A-region) extended from the amino acid residues 219 to 464 of the PAc molecule is important in the binding of its surface protein to human salivary components and is possessed of the dominant antigenicity.
We, therefore, synthesized 24 sequential overlapping 19 residues-peptides covering the entirety of A-region and determined T and B cell epitopes on the peptides by using a series of B10 congenic mice. Until now, at least 3 kinds of T cell epitopes and 3 kinds of B cell epitopes were identified. The results clearly indicate that murien immune responses to the PAc are restricted by the MHC class II gene haplotypes.
Finally, to obtain the antigenic peptides for the passive immunization, the immunities of 16 synthetic peptides which contain the T and/or B cell epitopes were examined by immunization to the mice. The 5 of them, especially PAc(361-379) and PAc(391-409), can indue the production of antibodies against not only own peptide but also the native PAc molecule. These two antigenic peptides might be useful in the passive immunization for prevention of dental caries.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Tokuda,M.et al.: "Complete nucleotide sequence of the gene for a surface protein antigen of Streptococcus sobrinus." Infect.Immun.59. 3309-3312 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takahashi,I.et al.: "Genetic control of immune responses in mice to synthetic peptides of a Streptococcus mutans surface protein antigen." Infect.Immun.60. 623-629 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sato,S.et al.: "Construction of mutants of Actinobacillus actinomycetemcomitans defective in serotype b-specific polysaccharide antigen by insertion of transposon Tn916." J.Gen.Microbiol.138. 1203-1209 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Okahashi,N.et al.: "Identification of antigenic epitopes in an alanine-rich repeating region of a surface protein antigen of Streptococcus mutans." Infec.Immun.61. 1301-1306 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takahashi,I.et al.: "Molecular characterization of a negative regulator of Streptococcus sobrinus surface protein antigen gene." J.Bacteriol.175. 4345-4353 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nakai,M.et al.: "Saliva-binding region of Streptococcus mutans surface protein antigen." Infect.Immun.61. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Russell,M.W.et al.: "Genetically engineered vaccines:Prospects for oral disease prevention" Plenum Press,New York, (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Okahashi,N.,et al: "Identification of antigenic epitopes in an alanine-rich antigen of Streptococcus mutans." Imfect.Immun.61. 1301-1306 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tkahashi,I,et al.: "Molecular characterization of a negative regulator of Streptococcus sobrinus surface protein antigen gene." J.Bacter:ol. 175. 4345-4353 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakai,M.et.al.: "Saliva-binding region of Streptococcus mutans surface protein antigen." Infect.Immun.61in press. (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 岡橋 暢夫他: "合成ペプチドを用いたエピトープの同定法" 実験医学. 10. 85-89 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Sato et al.: "Construction of mutants of Actinobacillus actinomycetem-comitans defective serotype b specific polysaccharide antigen by insertion of transposon Tn916" Journal of General Microbiology. 138. 1203-1209 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Tokuda et al.: "Complete nucleotide sequence of the gene for a surface protein antigen of Streptococcus sobrinus" Infection and Immunity. 59. 3309-3312 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] I.Takahashi et al.: "Genetic control of immune responses in mice to svpthetic peptides of a Streptococcus mutans surface protein antigen" Infection and Immunity. 60. 623-629 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.W.Russell et al.: "Genetically Engineered Vaccines:Prospects for Oral Disease Prevention" Plenum Press,New York, (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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