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Construction of human monoclonal antibodies for passive immuno therapy of oral diseases using Xenomouse

Research Project

Project/Area Number 13357017
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionNihon University

Principal Investigator

ABIKO Yoshimitsu  Nihon University, School of Dentistry at Matsudo, Professor, 松戸歯学部, 教授 (70050086)

Co-Investigator(Kenkyū-buntansha) KISHIKAWA Michiko (KIYAMA Michiko)  Nihon University, School of Dentistry at Matsudo, Resarch Assistant (Full-Time), 松戸歯学部, 助手 (50256905)
SHIBATA Yasuko  Nihon University, School of Dentistry at Matsudo, Lecturer (Full-Time), 松戸歯学部, 講師 (90133438)
SAITO Shigeno  Nihon University, School of Dentistry at Matsudo, Lecturer (Full-Time), 松戸歯学部, 講師 (60072394)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥43,290,000 (Direct Cost: ¥33,300,000、Indirect Cost: ¥9,990,000)
Fiscal Year 2003: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2002: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2001: ¥32,110,000 (Direct Cost: ¥24,700,000、Indirect Cost: ¥7,410,000)
KeywordsHuman monoclonal antibody / Xenomouse / Transchromo mouse / Passive immunization / Periodontal diseases / Porphyromonas gingivalis / Streptococcus sobrinus / Xeno mouse / transchromo-mouse / 赤血球凝集因子 / 歯周病病原因子 / ヘミン結合活性 / ヒト型抗体 / 不溶性グルカン / GTF / 口腔感染症 / う蝕 / Mutans Streptococci
Research Abstract

The passive immunotherapy is a method for neutralizing the pathogenicity using antibody against each pathogen. Recently, it has been suggested that periodontal diseases are one of the consequential risk factors for several systemic diseases. As one of the medical treatments for the maintenance for human health, the development of passive immunotherapy for periodontal disease may be significant and necessary. Following research idea to construct the human monoclonal. antibodies (HmAbs) for the safety passive immunotherapy were carried out: Because the molecular information of the target antigens were important to use the HmAbs for passive immunotherapy, preliminary we attempted to clarify the molecule functional analysis of target antigens, such as hemagglutinin molecules and coaggregation factor of Porphyromonas gingivalis, and glucosyltransferases (GTFs) of Streptococcus sobrinus. Additionally, the large volume purification system by osmotic electrophoresis was also improved.
The HmAbs … More for passive immunity examined 1) the human lymphocyte immortalization method using EB virus, 2) the method, using Xenomouse, 3) the method using Transchromomouse, and hmAbs were produced using these methods. In addition, recombinant ScFv using mouse monoclonal antibody producing hybridoma cell was improved into the large-scale production system, moreover, IgY antibody by the chicken immunity was also produced. In this study, the, practicable abilities of clones were screening using a Biacore system to detect the mAbs levels and avidity in cultured medium. The constructed HmAbs ability was determined the neutralization levels against the pathogenicity of antigens.
Using Xenomouse technology, we succeeded to construct the HmAbs against the hemagglutinin of P. gingivalis, and GTFs of 」 sobrinus., Moreover, using Transchromomouse technology, HmAb against the coaggregation factor of P gingivalis was also constructed. Interestingly, the anti-coaggregation factor antibodies could increase the neutrophilic activity to phagocytize the P gingivlais cells. We also succeeded in the construction of IgY antibody against the hemagglutinin activity of P gingivalis. Less

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (63 results)

All 2003 Other

All Journal Article (2 results) Publications (61 results)

  • [Journal Article] A35-kDa co-aggregation factor is a hemin binding protein in Porphyromonas gingivalis.2003

    • Author(s)
      Yasuko Shibata
    • Journal Title

      Biochemical and Biophysical Research Communications 300・2

      Pages: 351-356

    • Related Report
      2002 Annual Research Report
  • [Journal Article] Human monoclonal antibody inhibits Porphyromonas gingivalis hemagglutinin activity2003

    • Author(s)
      Kouji Kaizuka
    • Journal Title

      Journal of Periodontology 74・1

      Pages: 38-43

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Shiroza: "Construction of a chimeric shuttle plasmid via a heterodimer system : Secretion of an scFv protein from Bacillus brevis cells capable of inhibiting hemagglutination."Biosci.Biotechnol.Biochem. 65. 389-395 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Hayakawa: "Evaluation of the electroosmotic medium pump system for preparative disk gel electrophoresis"Anal.Biochem.. 288. 168-175 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N.Shinozaki-Kuwahara: "Purification and Characterization of an oligo-isomaltosaccharide synthase from a Streptococcus sobrinus glucosyltransferase-I deficient mutant"Biosci.Biotechnol.Biochem.. 65. 1290-1295 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Koreeda: "Isolation and characterisation of dipeptidyl peptidase IV from Prevotella loescheii ATCC 15930."Arch.Oral Biol.. 46. 759-766 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Hosogi: "Monoclonal antibody against Porphyromonas gingivalis hemagglutinin inhibits hemolytic activity."Eur.J.Oral Sci.. 109. 109-113 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Abiko: "Inhibition of hemolysis by antibody against the Porphyromonas gingivalis 130-kDa hemagglutinin domain."J.Oral Sci.. 43. 159-163 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Otsuka: "Enhancement of plasminogen activator activity stimulated by LPS in gingival fibroblasts of individuals with down syndrome"J.Oral Sci.. 43. 207-212 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] E.Nonaka: "Identification of 40-kDa outer membrane protein as an aggregation factor of Porphyromonas gingivalis to Streptococcus gordonii."J.Oral Sci.. 43. 239-243 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N.Hanada: "Cloning and nucleotide sequence analysis of the Streptococcus sobrinus gtfU gene that produces a highly branched water-soluble glucan"Biochim.Biophys.Acta. 1570. 75-79 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Kurosawa: "Characterization of rat monoclonal antibodies against human β-defensin-2."Hybridoma and Hybridomics. 21. 359-363 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Kaizuka: "Human monoclonal antibody inhibits Porphyromonas gingivalis hemagglutinin activity."J.Periodontol.. 74. 38-43 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Shibata: "A 35-kDa co-aggregation factor is a hemin binding protein in Porphyromonas gingivalis."Biochem.Piophys.Res.Commun.. 300. 351-356 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Hayakawa: "Determination of short peptide in a Porphyromonas gingivalis protein antigen recognized by sera from periodontitis patients."Int.J.Oral-Med.Sci.. 1. 79-81 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Otsuka: "Enhancement of lipoplysaccharide-stimulated cyclooxygenase-2 mRNA expression and prostaglandin E2 production in gingival fibroblasts from individual with Down syndrome."Mecha.Age.Dev.. 123. 663-674 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Hayakawa: "Further development of an electroosmotic medium pump system for preparative disk gel electrophoresis"Anal.Biochem.. 313. 60-67 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Shiroza: "Production of a single-chain variable fraction capable of inhibiting the Streptococcus mutans glucosyltransferase in Bacillus brevis. Construction of chimeric shuttle plasmid secreting its gene product."Biochimica et Biophysica Acta. 1626. 57-64 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Tsurumi: "Production of antibody against a synthetic peptide of Porphyromonas gingivalis 40-kDa outer membrane protein."J.Oral Sci.. 45. 111-116 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Teshirogi: "Production of monoclonal antibody inhibiting dipeptidylaminopeptidase IV activity of Porphyromonas gingivalis"Hybridoma Hybridomics. 22. 147-151 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Ema: "Characterization of the gene encoding 200-kDa Prophyromonas gingivalis protein that reacts to sera from periodontitis patients."J.Oral Sci.. 45. 145-152 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Yamada: "Identification of the functional domain in a coaggregation factor from Porphyromonas gingivalis."Int.J.Oral-Med.Sci.. 1. 97-102 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Abiko: "Analysis of functional domains of Streptococcus sobrinus glucosyltransferase U."Int.J.Oral-Med.Sci.. 1. 152-156 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Namikoshi: "Nasal Immunization with P.gingivalis surface protein antigen and cholera toxin adjuvant induces T helper 2 responses in both mucosal and systemic compartments."Int.J.Oral-Med.Sci.. 1. 90-96 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Hayakawa: "Large-scale preparative disk gel electrophoresis with electroosmotic medium pump system."J.Electrophoresis.. 47. 151-154 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Namikoshi: "Specific antibodies induced by nasally administered 40-kDa outer membrane protein of Porphyromonas gingivalis inhibits coaggregation activity of P.gingivalis."Vaccine. 22. 250-256 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Abiko: "Induction of hemagglutination by recombinant Porphyromonas gingivalis 40-kDa outer membrane protein."Int.J.Oral-Med.Sci.. 2. 54-56 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Tagawa: "Production of Functional ScFv Inhibiting Streptococcus mutans Glucosyltransferase Activity from a Hybridoma P126."Hybridom.Hybridomic.. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Shiroza, et al.: "Construction of a chimeric shuttle plasmid via a heterodimer system : Serection of an scFv protein from Bacillus brevis cells capable of inhibiting hemagglutination."Biosci.Biotechnol.Biochem.. Vol.65,No.2. 389-395 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Hayakawa, et al.: "Evaluation of the electroosmotic meium pump system for preparative disk gel electrophoresis."Anal.Biochem.. Vol 288. 168-175 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N.Shinozaki-Kuwahara, et al.: "Purification and Characterization of an oligo-isomaltosaccharide syndhase from a Streptococcus sobrinus glucosyltransferase-I deficeitn mutant."Biosci.Biotechnol.Biochem.. Vol.65,No.6. 1290-1295 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Koreeda, et al.: "Isolation and characterisation of dipepdidyl peptidase IV from Prevotella loescheii ATCC 15930."Arch.Oral Biol.. Vol 46. 759-766 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Hosogi, et al.: "Monoclonal antibody against Porphyromonas gingivalis hemagglutinin inhibits hemolytic activity."Eur.J.Oral Sci.. Vol.109. 109-113 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Abiko, et al.: "Inhibition of hemolysis by antibody against the Porphyromonas gingivalis 130-kDa hemagglutinin domain"J.Oral Sci.. Vol.43,No.3. 159-163 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Otsuka, et al.: "Enhancement of plasminogen activator activity stimulated by LPS in gingival fibroblasts of individuals with down syndrome."J.Oral Sci.. Vol.43,No.3. 207-212 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] E.Nonaka, et al.: "Identification 9f40-kDa outer membrane protein as an aggregation factor of Porphyromonas gingivalis to Streptococcus gordonii."J.Oral Sci.. Vol.43,No.4. 239-243 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N.Hanada, et al.: "Clonign and nucleotide sequence analysis of the Streptococcus sobrinus gtfU gene that produces a highly branched water-soluble glucan."Biochim.Biophys.Acta. Vol.1570. 75-79 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Kurosawa, et al.: "Characterization of rat monoclonal antibodies agaisnt human b-defensin-2."Hybridoma and Hybridomics. Vol.21,No.5. 359-363 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Kaizuka, et al.: "Human monoclonal antibody inhibits Porphyromonas gingivalis hemagglutinin activity"J.Periodontol.. Vol.74. 38-43 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Shibata, et al.: "A 35-kDa co-aggregation factor is a hemin binding protein in Porphyromonas gingivalis."Biochem.Piophys.Res.Commun.. Vol.300. 351-356 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Hayakawa, et al.: "Determination of short peptide in a Porphyromonas gingivalis protein antigen recognized by sera from periodontitis patients."Int.J.Oral-Med.Sci.. Vol.1,No.1. 79-81 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Otsuka, et al.: "Enhancement of lipoplysaccharide-stimulated cyclooxygenase-2 mRNA expression and prostaglandin E2 production in gingival fibroblasts from individual with Down syndrome."Mecha.Age.Dev.. Vol.123. 663-674 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Hayakawa, et al.: "Further development of an electroosmotic medium pump system for preparative disk gel electrophoresis."Anal.Biochem.. Vol.313. 60-67 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Shiroza, et al.: "Production of a single-chain variable fraction capable of inhibiting the Streptococcus mutans glucosyltransferase in Bacillus brevis. Construction of chimeric shuttle plasmid secreting its gene product."Biochmimic Biopysica Acta. Vol 1626. 57-64 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Tsurumi, et al.: "Production of antibody against a synthetic peptide of Porphyromonas gingivalis 40-kDa outr membrane protein"J.Oral Sci. Vol.45,No.. 111-116 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Teshirogi, et al.: "Production of monoclonal antibody inhibiting dipeptidylaminopeptidase IV activity of Porphyromonas gingivalis."Hybridoma Hybridomics. Vol.22,No.3. 147-151 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Ema, et al.: "Characterization of the gene encoding 200-kDa Prop hyromonas gingivalis protein that reacts to sera from periodontitis patients."J.Oral Sci.. Vol 45,No.3. 145-152 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Yamada, et al.: "Identification of the functional domain in a coaggregation factor from Porphyromonas gingivalis."Int.J.Oral-Med Sci. Vol.1,No.2. 97-102 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Abiko, et al.: "Analysis of functional domains of Streptococcus sobrinus glucosyltransferase U."Int.J.Oral-Med.Sci.. Vol.1,No.2. 152-156 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Namikoshi et al.e: "Nasal Immunization with P gingivalis surface protein antigen and cholera toxin adjuvant induces T helper 2 responses in both mucosal and systemic compartments."Int.J.Oral-Med Sci.. Vol.1,No.2. 90-96 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Hayakawa, et al.: "Large-scale preparative disk gel electrophoresis with electroosmotic medium pump system."J.Electrophoresis. Vol.47. 151-154 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Namikoshi, et al.: "Specific antiboies induced by nasally administered 40-kDa outer membrane protein of Porphyromonas gingivalis inhibits coaggregation activity of gingivalis."Vaccine. Vol.22. 250-256 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Abiko, et al.: "Induction of hemagglutination by recombinant Porphyromonas gingivalis 40-kDa outer membrane preotein."Int.J.Oral-Sci. Vol.2,No.1. 54-56 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Tagawa, et al.: "Production of Functional ScFv Inhibiting Streptococcus mutans Glucosyltransferase Activity from a Hybridoma P126."Hybridom.Hybridomic.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shioza, T.et al.: "Production of a single-chain variable fraction capable of inhibiting the Streptococcus mutansglucosyltransferase in Bacillus brevis : Construction of a chimeric shuttle plasmid secretings its gene product"Biochimica Biophysica Acta. 1626. 57-64 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsurumi, Y.et al.: "Production of antibody against a synthetic peptide of Porphyromonas gingivalis 40-kDa outermembrane protein"Journal of Oral Science. 78(2). 111-116 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Teshirogi, K.et al.: "Production of monoclonal antibody inhibiting dipeptidylaminopeptidase IV activity of Porphyromonas gingivalis"Hybridoma and Hybridomics. 22(3). 147-151 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ema, M.et al.: "Characterization of the gene encoding 200-kDa Porphyromonas gingivalis protein that react to sera from periodontitis patients"Journal of Oral Science. 45(3). 145-152 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada, K., et al.: "Identification of the functional domain in a coaggregation factor from Porphyromonas gingivalis"International Journal of Oral-Med Sciences. 1(2). 97-102 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Abiko, Y.et al.: "Analysis of functional domains of Streptococcus sobrinus glucosyltransferase"International Journal of Oral-Med Sciences. 1(2). 152-156 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kaizuka K et al.: "Human Monoclonal Antibody Inhibit Porphyromonas gingivalis Hemagglutinin Activity"Journal of Periodontology. 74. 38-43 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shibata Y: "A 35-kDa co-aggregation factor as a hemin binding protein in Porphyromonas gingivalis"Biochemical Biophysical Research Communication. 300. 351-356 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 安孫子宜光他: "歯周病のストラテジー、第3編 11章 歯周病の遺伝子診断"医歯薬出版. 395 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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