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Synthesis of human Fab

Research Project

Project/Area Number 14406020
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field 内科学一般
Research InstitutionOita University

Principal Investigator

YAMASHIRO Tetsu  Oita University, Institute of Scientific Research, Associate Professor, 医学部・総合科学研究支援センター, 助教授 (00244335)

Co-Investigator(Kenkyū-buntansha) SONODA Yoshiko  Oita University, Institute of Scientific Research, Assistant Professor, 医学部・総合科学研究支援センター, 助手 (80253780)
MAKINO Yoshihiro  Oita University, Department of Infectious Diseases, Professor, 医学部, 教授 (60039930)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥4,500,000 (Direct Cost: ¥4,500,000)
Keywordscombinatorial science / phage display / dengue infection / tropical medicine / infectious diseases / humanized antibody / Antibody engineering / antibody therapy / ファージディスプレイ / 抗体 / デングウイルス / 抗体療法 / 分子生物学
Research Abstract

The sero-prevalence of dengue virus (DEN)-specific IgG was determined among 1008 adults and among 201 children younger than 10 years old, in Santo Domingo Dominican Republic Most adults (98%, 987/1008) and 56% (113/201) of children were positive for DEN-specific IgG. Among children, the prevalence of DEN-specific IgG increased with age, that is, 1 to 2 yr, 0--5%, 3 to 6 yr, 25 --65%, and 【greater than or equal】 7 yr, 76 --92%. Fifty percent of the prevalence shown in <1 group was probably due to maternal antibody transfer. Neutralization tests of adult samples indicate that DEN infections with different serotypes have occurred sequentially or simultaneously among the inhabitants of Santo Domingo. Fab monoclonal antibodies to DEN4 were recovered from mRNA from immune higher primate. Two Fabs neutralized DEN4 efficiently with a titer of 0.24-0.48 micro g/mL by PRNT. One of the Fab was converted to full-length IgG1 by combining it with human sequences. The humanized IgG1 neutralized DEN4 strains from different geographical origins at a similar PRNT50 titer. A human Fab library was constructed from PBL of volunteers who had recovered from severe DEN infection. The phage library was panned several times with DEN1, DEN2, DEN3, and DEN4 virions, and recombinant DEN4 NS1 protein, and Japanese encephalitis virus virion.

Report

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

    (9 results)

All Other

All Publications (9 results)

  • [Publications] R.Men, T.Yamashiro, et al.: "Identification of chimpanzee Fab fragments by repertoire cloning and production of a full-length humanized IgG1 antibody highly efficient for neutralization of dengue type 4 virus."Journal of virology. (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.Yamashiro, et al.: "Seroprevalence of IgG specific to Dengue virus among adults and children of Santo Domingo, Dominican Republic."American Journal of Tropical Medicine and hygiene. (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.Yamashiro: "Synthesis of useful antibody molecules using the combinatorial library and the phage display technologies"Jpn.J.Trop.Med.Hyg.. 31. 24-25 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] R.Men, T.Yamashiro, et al.: "Identification of chimpanzee Fab fragments by repertoire cloning and production of a full-length humanized IgG lantibody highly efficient for neutralization of dengue type 4 virus."Journal of Virology. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Yamashiro, et al.: "Seroprevalence of IgG specific to Dengue virus among adults and children of Santo Domingo, Dominican Republic."American Journal of Tropical Medicine and hygiene. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Yamashiro: "Synthesis of useful antibody molecules using the combinatorial library and the phage display technologies."Jpn.J.Trop.Med.Hyg.. 31. 24-25 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Men, R., Yamashiro, T.et al.: "Identification of chimpanzee Fab fragments by repertoire cloning and Production of a full-length humanized IgG1 antibody highly efficient for neutralization of"Journal of Virology. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamashiro, T.: "Seroprevalence of IgG specific to Dengue virus among adults and children of Santo Domingo, Dominican Republic"American Journal of Tropical Medicine and Hygiene. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamashiro, T.: "Synthesis of useful antibody molecules using the comnibatorial library and the Phage display technologies"Japanese Journal of Tropical Medicine and hygiene. 31. 24-25 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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