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Development of Anti-Dental Caries Vaccine Using Recombinant Lactic Streptococci

Research Project

Project/Area Number 63870086
Research Category

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

Allocation TypeSingle-year Grants
Research Field 小児・社会系歯学
Research InstitutionNational Institute of Health

Principal Investigator

KOGA Toshihiko  N. I. H., Dept. Dent. Res., Director, 歯科衛生部, 部長 (10037541)

Co-Investigator(Kenkyū-buntansha) OHTA Hirotaka  Lion Co., Ist Res. Inst., Research Worker, 第一応用研究所, 研究員
TAKAHASHI Ichiro  N. I. H., Dept. Dent. Res., Research Worker, 歯科衛生部, 研究員 (20206791)
OKAHASHI Nobuo  N. I. H., Dept. Dent. Res., Chief, 歯科衛生部, 主任研究官 (40150180)
Project Period (FY) 1988 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 1990: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1989: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1988: ¥7,500,000 (Direct Cost: ¥7,500,000)
KeywordsDental Caries / Streptococcus mutans / Streptococcus sobrinus / Lactic Streptococci / Vaccine / DNA組換え / う蝕
Research Abstract

Streptococcus mutans has been implicated as a causative organism of human dental caries. S. Mutans produces a cell surface protein antigen (PAc) with a molecular mass of 190 kilodaltons. In this study, we constructed a recombinant lactic streptococcus with carries th pac gene of S. Mutans for development of an oral vaccine against dental caries.
1. We cloned the pac gene of S. Mutans MT8148 (serotype c) and determined the complete nucleotide sequence of the gene. The pac gene consisted of 4,695 base pairs. The initial gene product contained 1,565 amino acids and had a molecular weight of 170,773.
2. To make clear the biological function of PAc, we constructed genetically several PAc-defective transformants fo S. mutans. The cell hydrophobicity of PAc-defective transformants was markedly lower than that of the parent strain. Resting cells of the hydrophilic strains attached in lower number to saliva-coated hydroxyapatite than did the parent strain. These findings suggest that cell surface PAc of S. Mutans participates in attachment of the streptococcal cell to aquired pellicles on tooth surfaces.
3. Homology between PAc of S. Mutans and a 210-kilodalton protein antigen of Streptococcus sobrinus was high in the central regions.
4. The pac gene from S. mutans was joined to shuttle vector pSA3. The chimeric plasmid pSM1 was successfully transformed into Streptococcus lactis. The recombinant S. Lactis produced a small amount of PAc. Significant salivary immunoglobulin A and serum immunoglobulin G responses to PAc were induced in mice immunized orally with the recombinant S. lactis.

Report

(4 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • 1988 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] N.Okahashi et al.: "Cloning of a surface protein antigen from serotype c Streptococcus mutans" Molecular Microbiology. 3. 221-228 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] S.Hamada et al.: "Purification and characterization of waterーinsoluble glucan synthesiszing cellーassociated glucosyltransferase of serotype c Streptococcus mutans" Journal of General Microbiology. 135. 335-344 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] H.Ohta et al.: "Characterization of a cellーsurface protein antigen of hydrophilic Streptococcus mutans strain GSー5" Journal of General Microbiology. 135. 981-988 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] N.Okahashi et al.: "Molecular characterization of a surface protein antigen gene from serotype c Streptococcus mutance,implicated in dental caries" Molecular Microbiology. 3. 673-678 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] I.Takahashi et al.: "Homology between surface protein antigen genes of Streptococcus sobrinus and Streptococcus mutans" FEBS Letters. 249. 383-388 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T.Koga et al.: "Effect of subculturing on expression of a cellーsurface protein antigen by Strptococcus mutans" Journal of General Microbiology. 135. 3199-3207 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T.Koga et al.: "Surface hydrophobicity,adherence,aggregation of cellーsurface protein antigen mutants of Streptococcus mutans serotype c" Infection and Immunity. 58. 289-296 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] F.Ota et al.: "Crossーreactive polysaccharide antigens (types a,d,and h)of the mutans group of streptococci:different molecular forms of the types as distiguishable by monoclonal antibodies" Zentralblatt fur Bakteriologie. 272. 294-305 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] M.Iwaki et al.: "Oral immunization with recombinant Streptococcus lactis carring the Streptococcus mutans surface protein antigen gene" Infection and Immunity. 58. 2929-2934 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] N.Okahashi et al.: "Construction of a NotI restriction map of the Streptococcus mutans genome" Journal of General Microbiology. 136. 2217-2223 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] I.Takahashi et al.: "Intranasal immunization with recombinant protein antigen of serotype c Streptococcus mutans and cholera toxin B subunit" Archives of Oral Biology. 35. 475-477 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] I.Takahashi et al.: "Immunogenicity and protective effect against oral colonization by Streptococcus mutans by synthetic peptides of a streptococcal surface protein antigen" Journal of Immunology. 146. 332-336 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] N. Okahashi et al: "Cloning of a surface protein antigen from serotype c Streptococcus mutans." Molecular Microbiology. 3. 221-228 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] S. Hamada et al: "Purification and characterization of water-insoluble glucan synthesizing cell-associated glucosyltransferase of serotype c Streptococcus mutans." Journal of General Microbiology. 135. 335-344 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] H. Ohta et al: "Characterization of a cell-surface protein antigen of hydrophilic Streptococcus mutans strain GS-5." Journal of General Microbiology. 135. 981-988 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] N. Okahashi et al: "Molecular characterization of a surface protein antigen gene from serotype c Streptococcus mutans, implicated in dental caries." Molecular Microbiology. 3. 673-678 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] I. Takahashi et al: "Homology between surface protein antigen genes of Streptococcus sobrinus and Sreptococcus mutans." FEBS Letters. 249. 383-388 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T. Koga et al: "Effect of subculturing on expression of a cell-surface protein antigen by Streptococcus mutans." Journal of General Microbiology. 135. 3199-3207 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T. Koga et al: "Surface hydrophobicity, adherence, aggregation of cell-surface protein antigen mutants of Streptococcus mutans serotype" Infection and Immunity. 58. 289-296 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] F. Ota et al: "Cross-reactive polysaccharide antigen (type a, d, and h) of the the mutans group of streptococci : different molecular forms of the types as distinguishable by monoclonal antibodies." Zentralblatt fur Bakteriologie. 272. 294-305 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] M. Iwaki et al: "Oral immunization with recombinant Streptococcus lactis carring the Streptococcus mutans surface protein antigen gene." Infection and Immunity. 58. 2929-2934 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] N. Okahashi et al: "Construction of a NotI restriction map of the Streptococcus mutans genome." Journal of General Microbiology. 135. 2217-2223 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] I. Takahashi et al: "Intranasal immunization with recombinant protein antigen of serotype c Streptococcus mutans and cholera toxin B subunit." Archives of Oral Biology. 35. 475-477 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] I. Takahashi et al: "Immunogenicity and protective effect against oral colonization by Streptococcus mutans by synthetic peptides of a streptococcal surface protein antigen." Journal of Immunology. 146. 332-336 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] I.Takahashi et al.: "Intranasal immunization with recombinant protein antigen of serotype c <Streptococcus>___ー <mutans>___ー and chorea toxin B subunit" Archives of Oral Biology. 35. 475-477 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] F.Ota et al.: "Crossーreactive polysaccharide antigens (types a,d,and h) of the the mutans group of streptococci:different molecular forms of the type as distinguishable by monoclonal antibodies" Zentralblatt Bakteriologie. 272. 294-305 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Iwaki et al.: "Oral immunization with recombinant <Streptococcus>___ー <lactis>___ー carring the <Streptococcus>___ー <mutans>___ー surface protein antigen gene" Infection and Immunity. 58. 2929-2934 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] N.Okahashi et al.: "Construction of a <NotI>___ー restriction map of the <Streptococcus>___ー <mutans>___ー genome" Journal of General Microbiology. 136. 2217-2223 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] I.Takahashi et al.: "Immunogenicity and protective effect against oral colonization by <Streptococcus>___ー <mutans>___ー by synthetic peptides of a streptococcal surface protein antigen" Jouranal of Immunology. 146. 332-336 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 古賀 敏比古ら: "う蝕細菌の病原因子" BIOmedia. 6. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] N.Okahashi et al.: "Cloning of a surface protein antigen from serotype c Streptococcus mutans" Molecular Microbiology. 3. 221-228 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] N.Okahashi et al.: "Nucleotide sequence of a surface protein antigen gene from serotype c Streptococcus mutans" Molecular Microbiology. 3. 673-678 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] H.Ohta et al.: "Characterization of a cellーsurface protein antigen of hydrophilic Streptococcus mutans strain GSー5" Journal of General Microbiology. 135. 981-988 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Koga et al.: "Effect of subculturing on expression of a cellーsurface protein antigen by Streptococcus mutans" Journal of General Microbilogy. 135. 3199-3207 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] I.Takahashi et al.: "Homology between surface protein antigen genes of Streptococcus sobrinus and Streptococcus mutans" FEBS Letters. 249. 383-388 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Koga et al.: "Surface hydrophobicity,adherence,and aggregation of cell surface protein antigen mutants of Streptococcus mutans serotype c" Infection and Immunity. 58. 289-296 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] 岡橋暢夫ら: "遺伝子からみた細菌の病原性" 菜根出版, 313 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 古賀敏比古: 日本歯科評論. 543. 129-139 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 岡橋暢夫: 微生物. 4. 3-12 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 高橋一郎: 日本歯科評論. 555. 153-162 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] H.Ohta et al.: Journal of General Microbiology. 135. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] N.Okahashi et al.: Molecular Microbiology. 3. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] N.Okahashi et al.: 4. 1989.

    • Related Report
      1988 Annual Research Report
  • [Publications] 寺脇誠致ら: "病原細菌遺伝子研究の新展開" 菜根出版, (1989)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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