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Identification of HTLV-1 neutralizing epitopes and the development of an HTLV-1 peptide based vaccine

Research Project

Project/Area Number 04670391
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内科学一般
Research InstitutionKyushu University

Principal Investigator

NAKAMURA Minoru  Kyushu University, Faculty of Medicine, Research Associte, 医学部, 助手 (40217906)

Co-Investigator(Kenkyū-buntansha) NAKANO Shuji  Kyushu University, Faculty of Medicine, Research Associte, 医学部, 助手 (40164248)
永渕 正法  九州大学, 医学部, 助手 (00150441)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsB lymphocyte repertoire / human monoclonal antibody / anti-HTLV-1 antibody / neutralizing epitope / peptide based vaccine / B cell epitope / T cell epitope / anti-mitochondrial antibody / 抗HTLV-1 抗体 / B Cell エピトープ / T Cell エピトープ / 抗HTLV-I抗体 / B cell エピトープ / T-cell エピトープ
Research Abstract

We have generated a number of human monoclonal antibodies(mAb) to HTLV-1 by transforming B lymphocyte with EBV.Peripheral blood obtained from patients with HAM/TSP was used as a source of B lymphocytes committed to the production of IgG antibodies to HTLV-1. By using these mAb, we have identified the principle linear neutralizing B cell epitopes of HTLV-1 on the envelope protein gp46 a.a.187-199. Thus, we proposed that this region would be a good candidate for a peptide based HTLV-1 vaccine. In order to develop a peptide based vaccine which can induce a high titer of neutralizing antibodies against HTLV-1, we first synthesized peptides of various lengths containing an a.a.sequence of the principle neutralizing determinant of HTLV-1 gp46 a.a.187-199. Then, we conjugated these peptides with MAP.High titers of neutralizing antibodies were induced by immunization of MAP181-210 in various strains of rats and rabbits. We also identified the major T cell epitope on gp46 a.a.194-210 in various strains of rats Furthermore, MAP181-210 contains a T cell helper epitope on a.a.194-210 in humans with various HLA haplotypes. It is therefore possible that MAP181-210 could become one of the first candidates of a peptide based vaccine for human use.

Report

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

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Eishi Baba and Minoru Nakamura et.al: "A peptide based HTLV-1 vaccine containing T and B cell epitopes which induces high titers of neutralizing antibodies." The Journal of Immunology. (in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minoru Nakamura et al: "Peripheral B lymphocyte repertoire to mitochondrial antigens in patients with primary biliary cirrhosis.-positive correlation between the disease activity and the freguency of circulating B lymphocytes committed to the production of IyG to AMA." Hepatology. (in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Jun-ichi Kira et al: "Sequence heterogeneity of HTLV-1 proviral DNA in the central nervous system of patients with HTLV-1 associated myelopathy." Annuals of Neurology. (in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hideyuki Ikematsu et al: "VH and VK segment structure of anti-Insulin IyG autoantibodies in patients with lnsulin-dependent diabetes mellitus.Evidence for somatic mutation." The Journal of Immunology. (in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mieko Matsui and Minoru Nakamura et al: "Human monoclonal autoantibodies from a patient with primary blliary cirrhosis which recognize two distinct autoepitoges in the E2 component of the pyruvate dehydrogenase complex." Hepatology. 18. 1069-1077 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Eishi Baba and Minoru Nakamura et al: "Multiple neutralizing B cell epitopes of HTLV-1 identified by human monoclonal antibodies.-A basis for the design of an HTLV-1 peptide vaccine-" The Journal of Immunology. 151. 1013-1024 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mika Kuroki and Minoru Nakamura et al: "Identification of new epitopes recognized by human monoclonal antibodies with neutrallzing and antibody-dependent cellular cytotoxicity activities specific for HTLV-1." The Journal of Immunology. 149. 940-948 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minoru Nakamura and Paolo Casali: "Generation of human monoclonal autoantibody-producing cell lines by Epstein-Barr virus(EBV)-transformation of autoreactive B lymphocytes followed by somatic cell hybridization." Immunomethods,Acodemic Press,Inc.San Diego.USA, 159-168 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Eishi Baba and Minoru Nakamura et al: "A peptide based HTLV-1 vaccine containing T and B cell epitopes which induce high titers of neutralizing antibodies." J.Immunol. (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minoru Nakamura et al: "Peripheral B lymphocyte repertoire to mitochondrial antigens in patients with primary biliary cirrhosis." Hepatology. (in press). (1944)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Jun-ichi Kira et al: "Sequence heterogeneity of HTLV-1 proviral DNA in the central nervous system of patients with HTLV-1 associated myelopathy." Annuals of Nneurology. (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hideyuki Ikematsu et al: "VH and VK segment structure of anti-insulin IgG autoantibodies in patients with insulin-dependent diabetes mellitus." J.Immunol. (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mieko Matsui and Minoru Nakamura et al: "Human monoclonal autoantibodies in a patient with primary biliary cirrhosis which recognize two distinct autoepietopes in the E2 component of the pyruvate dehydrogenase complex." Hepatology. 18. 1069-1077 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Eishi Baba and Minoru Nakamura et al: "Multilpe neutralizing B cell epotopes of HTLV-1 identified by human monoclonal antibodies. - A basis of the design of an HTLV-1 peptide vaccine -" J.Immunol. 151. 1013-1024 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mika Kuroki and Minoru Nakamura et al: "Identification of new epitopes recognized by human monoclonal antibodies with neutralizing and antibody-dependent cellular cytotoxicity activities specific for HTLV-1." J.Immunol. 149. 940-948 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minoru Nakamura et al: "Increase of peripheral B lymphocytes committed to the production of monoreactive and high affinity antibodies to HLTV-1 in patients with HAM/TSP." J.Neuroimmunol.37. 35-45 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minoru Nakamura and Paolo Casali: "Generation of human monoclonal autoantibody-producing cell lines by Epstein Barr virus-transformation of autoreactive B lymphocytes followed by somatic cell hybridization." Immunomethods. 1. 159-168 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Eishi,Baba and Minoru,Nakamura et al.: "A peptide based HTLV-1 vaccine containing T and B cell epitopes which induces high titers of neutralizing antibodies." The Journal of Immunology. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Minoru,Nakamura et al.: "Peripheral B lymphocyte repertoire to mitochondrial antigens in patients with primery biliary cirrhosis.-Positive correlation between the disease activity and the frecuency of ." Hepatology. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Jun-ichi,Kira et al.: "Sequence heterogeneity of HTLV-1 proviral DNA in the central nervous system of patients with HTLV-1 associated myelopathy." Annuals of Neurology. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hideyuki,Ikematsu et al.: "VH and VK segment structure of anti-Insulim Ig G autoantibodies in patients with insulin-dependent diabetesmellitus.Evidence for somatic mutation.21GC04:The Journal of Immunology." (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mieko,Matsui and Minoru,Nakamura et al.: "Human monocloxal autoantibodies apatient with primary biliary cirrhosiswhich recognize two distinct autoepitopes in the E2 component of the pyruvatedehydrogenase complex." Hepatology. 18. 1069-1077 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Eishi,Baba and Minoru,Nakamura et al.: "Multiple neutralizing B cell epitopes of HTLV-1 identified by human monoclonal antibodies.-A basis for the design of an HTLV-1 peptide vaccine-." The Journal of Immunology.151. 1013-1024 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mika,Kuroki and Minoru,Nakamuraet al.: "Identification of new epitopes recognized by human monoclonal antibodies with neutralizing and antibody-dependent cellular cytotoxicity activities specific for HTLV-1." The Journal of Immunology.149. 940-948 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Minoru,Nakamura and Paoro,Casali.: "Generation of human monoclonal autoantibedy-producing cell lines by Epstein-Barr virus(EVB)-transformation ofautoreactive B lymphocytes followed bysomatic cell hybridization." Immunomethods,Academic Press,Inc.San Diego U.S.A., 159-168 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Minoru Nakamura: "Elevated antibodies to synthetic peptides of HTLV-I envelope transmembrane glycoproteins with HAM/TSP." Journal of Neuroimmunology. 35. 167-177 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Minoru Nakamura: "Increase of peripheral B lymphocytes committed to the production of monoreactive-and high affinty-antibodies to HTLV-I in patients with HAM/TSP." Journal of Neuroimmunology. 37. 35-45 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Jun-ichi Kira: "Antibodies titers to HTLV-I p40 tax protein and gag-env hybrid protein in HTLV-I-associated myelopathy/tropical spastic paraparesis:correlation with increased HTLV-I proviral DNA load." Journal of the Neurological Sciences. 107. 98-104 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mika-Kuroki: "Identification of new epitopes recognized by human monoclonal antibodies with neutrolizing and antibody-dependent cellular cytotoxicity activities specific for human T-cell leukemia virus type I." The Journal of Immunology. 149. 940-948 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mika-Kuroki: "In vivo comparative the rapeutic study of optimal adminitration of 5-fluorouracil and cisplatin using a newly establised HST-I human squamous-carcinoma cell line." Cancer Chemother Pharmacol. 29. 273-276 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Taito Esaki: "Inhibition by 5-fluorouracil of cis-diamminedichloroplatinum(II)-induced DNA interstrand cross-link removal in a HST-I humam squamous carcinoma cell line" Cancer Research. 52. 6501-6506 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kenji Mitsugi: "Simple and efficient chemosensitivity assay for human primary cells using contact-sensitive microtiter plates" International Journal of oncology. 1. 141-147 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Minoru Nakamura: "Generation of human monoclonal autoantibody-producing cell lines by Epstein-Barr virus(EBV)-transformation of autoreactive B lymphocytes followed by somatic cell hybridization." Immunomethods,Academic Press,Inc.San Diego,U.S.A., IN PRESS

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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