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Immunopotentiation by immunoadjuvants of human viral vaccines

Research Project

Project/Area Number 04304033
Research Category

Grant-in-Aid for Co-operative Research (A)

Allocation TypeSingle-year Grants
Research Field Immunology
Research Institution(Institute of Immunological Science) Hokkaido University

Principal Investigator

AZUMA Ichiro  Hokkaido University, Institute of Immunological Science, Professor, 免疫科学研究所, 教授 (50028411)

Co-Investigator(Kenkyū-buntansha) YAMANISHI Koichi  Osaka University, Research Institute of Microbial Diseases, Professer, 微生物病研究所, 教授 (10029811)
MATSUURA Motohiro  Jichi Medical School.Department of Microbiology, Associate Professor, 医学部, 助教授 (20150089)
TOKURA Seiichi  Hokkaido University, Graduate School of Environmental Earth Science, Professor, 大学院・地球環境科学研究科, 教授 (40000806)
ISHIZUKA Masaaki  Microbial Chemistry Research Foundation, Institute for Chemotherapy, Vice-direct, 付属化学療法研究所, 副所長 (80159722)
IKUTA Kazuyoshi  Hokkaido University, Institute of Immunological Science, Professor, 免疫科学研究所, 教授 (60127181)
有川 二郎  北海道大学, 免疫科学研究所, 助教授 (10142704)
大隈 邦夫  化学及血清療法研究所, 課長
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥17,000,000 (Direct Cost: ¥17,000,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1993: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1992: ¥8,000,000 (Direct Cost: ¥8,000,000)
KeywordsMuramyldipeptide derivatives / Microbial-derived immunomodulators / Artificial polysaccharide immunoadjuvants / Lipid A derivatives / Synthetic DNA / Hanta virus / Component vaccine of influenza virus / HIV-6
Research Abstract

Recently, great advances have been made in the field of the developments of viral vaccines, especially recombinant proteins, synthetic peptides and purified components of viruses were developed as vaccines. These recombinant protein and synthetic peptide vaccines were shown to have weak antigenicity as vaccines and the application of effective immunoadjuvants is essentially required. In this research projects, both MDP derivatives, MDP-Lys(L18)and B30-MDP were reported to be effective adjuvants for vaccines. B30-MDP was shown to be effective for the potentiation of antigenicity of component vaccine of influenza virus and type B hepatitis recombinant vaccine. It was also found that MDP-Lys(L18)is effective as adjuvant in recombinant vaccine of type B hepatitis virus when both adjuvant and antigen were mixed as water solution and immunized in mice. B30-MDP was also shown to have adjuvant actibity for the production of circulating antibody and cell-mediated immunity to in activated vaccine and recombinant nuclear protein of Hanta virus. GLA-60, lipid A-related compound, was shown to have also potent adjuvant activity in recombinant type B hepatitis vaccine.
In this research project we have continued the study on the development of new immunoadjuvants for the vaccine, and several adjuvant-active substances such as chitosan oligomer, conagenin, synthetic DNA,teichoic acid, have been developed. As the antigens of virus vaccine development, the recombinant surface protein and nuclear protein of Hanta virus were prepared by recombinant gene technology. The infection models and antigenic analysis of HIV-1, HIV-6 and Hanta viruses were examined and the efficacy of immunoadjuvant to theses infection models is also discussed.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] Ichiro Azuma: "Effects of muramyldipeptide derivatives as adjuvants on the induction of antibody response to recombinant hepatitis B surface antigen." Vaccine. 13. 77-82 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kazuyoshi Ikuta: "In vivo induction of human immunodificiency virus type 1-specific cytotoxic T lymphocytes and delayed-type hypersensitivity by a 23-amino acid peptide from the highly conserved region in major core protein p24." Vaccine. 12. 485-491 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masaaki Ishizuka: "Biosynthesis of antitumor antibiotic,cytogenin." The Journal of Antibiotics. 47. 440-446 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Seiichi Tokura: "Induction of drug spesific antibody and the controlled release of drug by 6-O-carboxymethyl chitin." J.Controlled Release. 28. 235-241 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Motohiro Matsuura: "Multistep regulation mechanisms for tolerance induction to lipopolysaccharide lethality in the tumor-necrosis-factor-α-mediated pathway:Application of non-toxic monosaccharide lipid A analogues for elucidation of mechanisms." Eur.J.Biochem.221. 335-341 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Koichi Yamanishi: "High rate of reactivation of human herpesvirus 6 in children with dengue hemorrhagic fever." The Journal of Infectious Diseases.170. 746-748 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ichiro Azuma: "Immunotherapy of Infections" Marcel Dekker, 191-203 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ichiro Azuma: "Adjuvants:Theory and Practical Applications" John Wiley&Sons Ltd., 239-264 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ichiro Azuma: "Effects of muramyldipeptide derivatives as adjuvants on the induction of antibody response to recombinant hepatitis B surface antigen." Vaccine. 13. 77-82 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kazuyoshi Ikuta: "In vivo induction of human immunodificiency virus type 1-specific cytotoxic T lymphocytes and delayd-type hypersensitivity by a 23-amino acid peptide from he highly tconserved region in major core protein p24." Vaccine. 12. 485-491 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masaaki Ishizuka: "Biosynthesis of antitumor antibiotic, cytogenin." The Journal of Antibiotics. 47. 440-446 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Seiichi Tokura: "Induction of drug specific antibody and the controlled release of drug by 6-O-carboxymethyl chitin." J.Controlled Release. 28. 235-241 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Motohiro Matsuura: "Multistep regulation mechanisms for tolerance induvtion to lipopolysaccharide lethality in the tumor-necrosis-factor-alpha-mediated pathway : Application of non-toxic monosaccharide lipid A analogues for elucidation of mechanisms." Eur.J.Biochem.221. 335-341 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Koichi Yamanishi: "High rate of reactivation of human herpesvirus 6 in children with dengue hemorrhagic fever." The Journal of Infectious Diseases.170. 746-748 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ichiro Azuma: "Immunotherapy of Infections" Marcel Dekker. 191-203 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ichiro Azuma: "Theory and Practical Applications" John Wiley & Sons Ltd.239-264 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ichiro Azuma: "Effects of muramyldipeptide derivatives as adjuvants in the induction of antibody response to recombinant hepatitis B surface antigen." Vaccine. 13. 77-82 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kazuyoshi Ikuta: "In vivo induction of human immunodificiency virus type 1-specific cytotoxic T lymphocytes and delayed-type hypersensitivity by a 23-amino acid peptide from the highly conserved region in major core protein p24." Vaccine. 12. 485-491 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masaaki Ishizuka: "Biosynthesis of antitumor antibiotic,cytogenin." The Journal of Antibiotics. 47. 440-446 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Seiichi Tokura: "Induction of drug specific antibody and the controlled release of drug by 6-O-carboxymethyl chitin." J.Controlled Release. 28. 235-241 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Motohiro Matsuura: "Multistep regulation mechaisms for tolerance induction to lipopolysaccharide lethality in the tumor-necrosis-factor-α-mediated pathway:Application of non-toxic monosaccharide lipid A analogues for elucidation of mechanisms." Eur.J.Biochem.221. 335-341 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Koichi Yamanishi: "High rate of reactivation of human herpesvirus 6 in children with dengue hemorrhagic fever." The Journal of Infectious Diseases.170. 746-748 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ichiro Azuma: "Immunotherapy of Infections" Marcel Dekker, 191-203 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ichiro Azuma: "Adjuvants:Theory and Practical Applications" John Wiley & Sons Ltd., 239-264 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Chiaki Ishihara: "Anti-viral activity of sulfated chitin derivatives against Friend murine leukaemia and herpes simplex type-1 viruses." Vaccine. 11. 670-674 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yung Choon Yoo: "MDP-Lys(L18),a lipophilic derivative of muramyl dipeptide,inhibits the metastasis of haematogenous and non-haematogenous tumours in mice." Vaccine. 12. 175-180 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yasumitsu Uraki: "Site specific binding of calcium ions to anionic chitin derivatives" Carbohydrate Polymers. 20. 139-143 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Longdi Ren: "Modification of chitin by ceric salt-initiated graft polymerisation-preparation of poly(methyl methacrylate)-grafted chitin derivatives that swell in organic solvents." Carbohydrate Polymers. 21. 23-27 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Jiro Arikawa: "Epizootiological studies of hantavirus infection among urban rats in Hokkaido Japan:evidences for the persistent infection from the sero-epizootiological surveys and antigenic characterizations of hantavirus isolates." Journal of Veterinary Medical Science. 56. 27-32 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kohji Ohki: "Characterization of a unique scrambled peptide derived from the CD4 CDR3-related region which shows substantial activity for blocking HIV-1 infection." Vaccine. 11. 682-686 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yoichi Fujii: "Evidence for the role of human immunodeficiency virus type 1 Nef protein as a grouth inhibitor to CD4+T lymphocytes and for the blocking of the Nef function by anti-Nef antibodies." Vaccine. 11. 837-847 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ichiro Azuma: "Adjuvants:Theory and Practical Applications" Butterworth-Heinemann Ltd.(in press), (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ichiro Azuma: "Immunotherapy of Infections" Marcel Dekker(in press), (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ichiro Azuma: "Synthetic immunoadjuvants:application to non-specific host stimulation and potentiation of vaccine immunogenicity." Vaccine. 10. 100-1006 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ichrio Azuma: "Development of cytokin-inducer romurtide;experimental study and dlinical application." Trends in Pharmacological Science. 13. 425-428 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Masahiko Kishi: "Cells surviving infection by human immunodeficiency virus type 1:vif or vpu mutants produce non-infectous or markedly less cytopathic viruses." Journal of General Virology. 73. 77-87 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kohji Ohki: "Human immunodeficiency virus type 1(HIV-1) superinfection of a cell clone converting it from prodrction of defective to infectious HIV-1 is mediated predominantly by CD4 regions other than thi major binding site for HIV-1 glycoproteins." Journal of General Virology. 73. 1761-1772 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Masahide Kaji: "Phase 1 clinical tests fo influenza MDP-virosome vaccine (KD-5382)." Vaccine. 10. 663-667 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Jiro Arikawa: "Protective role of antigenic sites ont he evelope protein of Hantaan virus defined by minoclonal antibodies." Archives of Virology. 126. 271-281 (1992)

    • Related Report
      1992 Annual Research Report

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

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