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Development of HIV-1 coreceptor-based HIV /AIDS defense vaccine

Research Project

Project/Area Number 16390023
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKumamoto University

Principal Investigator

SHOJI Shozo  Kumamoto University, Faculty of Medical and Pharmaceutical Science, Ph.D., Professor, 大学院医学薬学研究部, 教授 (60040317)

Co-Investigator(Kenkyū-buntansha) MISUMI Shogo  Kumamoto University, Faculty of Medical and Pharmaceutical Science, Ph.D., Professor, 大学院医学薬学研究部, 助教授 (40264311)
TAKAMUNE Nobutoki  Kumamoto University, Faculty of Medical and Pharmaceutical Science, Ph.D., Professor, 大学院医学薬学研究部, 助手 (60322749)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2006: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2005: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2004: ¥6,200,000 (Direct Cost: ¥6,200,000)
KeywordsHIV-1 / Vaccine / Coreceptor / UPA
Research Abstract

A cyclic chimeric dodecapeptide (cCD) mimicking the conformation-specific domains of CCR5 and CXCR4 was prepared in which Gly-Asplinkstheaminoandcarboxylterminioftwocombinedpentapeptides(S_<169>-G_<173> of CCR5 ; E_<179>-R_<183> of CXCR4) derived from human immunodeficiency virus type-1 (HIV-1) coreceptors. The immunization of Balb/c mice with cCD conjugated with a multiple-antigen peptide (cCD-MAP) induced seven cCD-specific monoclonal antibodies (mAbs, CPMAb-I to-VII) that reacted with native CCR5 and CXCR4. Among the tested mAbs, CPMAb-I and-II potently inhibited the infection of both the R5 and X4 laboratory strains. CPMAb-III and-V1wereeffectiveagainstonlyR5laboratorystrains, and also against some X4 and R5 primary isolates. CPMAb-IV and-Vhadpotent antiviral activities againsttheR5 and X4 primary isolates. In particular, CPMAb-VII was protective against not only R5 and X4 laboratory strains, but also most of the R5 and X4 primary isolates. Moreover, cCD-MAP immunization also induced antibodies that were effective against R5 and X4 multiclade HIV-1 isolates in vitro in two of three cynomolgus monkeys. Taken together, the results suggest that cCD-MAPisacandidatemulticladeimmunogenthatcanbeused to block multiclade R5 and X4 HIV-1 infections.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (11 results)

All 2006 2005 2004

All Journal Article (10 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Effects of Immunization with CCR5-Based Cycloimmunoger on Simian/HIVSF_<162P3> Challenge.2006

    • Author(s)
      Misumi S, Nakayama D, Kusaba, M, Iiboshi T, Mukai R, Tachibana K, Nakasone T, Umeda M, Shibats H, Endo M, Takamune N, Shoji S
    • Journal Title

      J Immunol. 176

      Pages: 463-471

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Immunoreactive cycloimmunogen design based on conformational epitopes derived from human immunodeficiency virus type 1 coreceptors : cyclic dodecapeptides mimic undecapeptidyl arches of extracellular loop-2 in chemokine receptor and inhibit human immunodeficiency virus type 1 infection.2006

    • Author(s)
      Shogo Misumi, Nobutoki Takamune, Shozo Shoji
    • Journal Title

      Endocrine, Metabolic & Immune Disorders - Drug Targets (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Effects of Immunization with CCR5-Based Cycloimmunogen on Simian/HIVSF162P3 Challenge.2006

    • Author(s)
      Misumi S, Nakayama D, Kusaba M, liboshi T, Mukai R, Tachibana K, Nakasone T, Umeda M, Shibata H, Endo M, Takamune N, Shoji S.
    • Journal Title

      J Immunol. 176

      Pages: 463-471

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Immunoreactive cycloimmunogen design based on conformational epitopes derived from human immunodeficiency virus type 1 coreceptors : cyclic dodecapeptides mimic undecapeptidyl arches of extracellular loop-2 in chemokine receptor and inhibit human immunodeficiency virus type 1 infection2006

    • Author(s)
      Shogo Misumi, Nobutoki Takamune, Shozo Shoji
    • Journal Title

      Endocrine, Metabolic & Immune Disorders-Drug Targets (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of immunization with CCR5-based cycloimmunogen on simian/HIV_<SF162P3> challenge.2006

    • Author(s)
      Misumi S, Nakayama D, Kusaba M, Iiboshi T, Mukai R, Tachibana K, Nakasone T, Umeda M, Shibata H, Endo M, Takamune N, Shoji S.
    • Journal Title

      J.Immunol. 176

      Pages: 463-471

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Suppression of multiclade R5 and X4 human immunodeficiency virus type-1 infections by a coreceptor-based anti-HIV strategy.2005

    • Author(s)
      Nakayama D, Misumi S, Mukai R, Tachibana K, Umeda M, Shibats H, Takamune N, Shoji S
    • Journal Title

      J Biochem. 138

      Pages: 571-582

    • NAID

      10017348202

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Suppression of multiclade R5 and X4 human immunodeficiency virus type-1 infections by a coreceptor-based anti-HIV strategy.2005

    • Author(s)
      Nakayama D, Misumi S, Mukai R, Tachibana K, Umeda M, Shibata H, Takamune N, Shoji S.
    • Journal Title

      J Biochem. 138

      Pages: 571-582

    • NAID

      10017348202

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Suppression of multiclade R5 and X4 human immunodeficiency virus type-1 infections by a coreceptor-based anti-HIV strategy.2005

    • Author(s)
      Nakayama D, Misumi S, Mukai R, Tachibana K, Umeda M, Shibata H, Takamune N, Shoji S.
    • Journal Title

      J.Biochem 138

      Pages: 571-582

    • NAID

      10017348202

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Inhibition of R5 HIV-1 infection HIV-1 infection with autoantibody against extracellular loop2 (ECL-2) in CCR52004

    • Author(s)
      Kusaba, M., S.Misumi, N.Takamune, S.Shoji et al.
    • Journal Title

      Seikagaku 76

      Pages: 872-872

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Antibody-mediated immiune strategy for blockade of multiclade R5 and X4 HIV-1 infections2004

    • Author(s)
      Tokunaga, K., S.Misumi, N.Takamune, S.Shoji et al.
    • Journal Title

      Seikagaku 76

      Pages: 871-871

    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 腸管免疫賦活剤2006

    • Inventor(s)
      庄司省三他3名
    • Industrial Property Rights Holder
      国立大学法人熊本大学
    • Filing Date
      2006-10-31
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

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