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Development of Broadly Reactive Influenza DNA Vaccine

Research Project

Project/Area Number 11470117
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Public health/Health science
Research InstitutionOsaka Prefectural Institute of Public Health

Principal Investigator

OKUNO Yoshinobu  Osaka Prefectural Institute of Public Health, Department of Public Health, Head of Division of Virology, 公衆衛生部, ウイルス課長 (30112064)

Co-Investigator(Kenkyū-buntansha) ITOH Masae  Osaka Prefectural Institute of Public Health, Department of Public Health, Senior researcher, 公衆衛生部, 主任研究員 (10201328)
KASE Tetsuo  Osaka Prefectural Institute of Public Health, Department of Public Health, Senior researcher, 公衆衛生部, 主任研究員 (10175276)
中川 直子  大阪府立公衆衛生研究所, 公衆衛生部, 主任研究員 (10280835)
前田 章子  大阪府立公衆衛生研究所, 公衆衛生部, 主任研究員 (40250279)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2001: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1999: ¥6,400,000 (Direct Cost: ¥6,400,000)
Keywordsinfluenza / DNA vaccine / hemagglutinin / neutralizing epitope
Research Abstract

Hemagglutinin protein (HA) of influenza virus is divided into two parts, the globular head and the stem regions, structurally. We have demonstrated that there is a conserved neutralizing epitope in the stem region of HA. To utilize the epitope we tried to construct the CDNA encoding headless HA, and it was applied for broadly reactive influenza DNA vaccine.
Before the previous year, the mice immunized with the DNA vaccine containing expression vector, PEF-BOS, did not induce effective immune responses against influenza virus. Therefore, this year the expression vector was replaced by pNOW-GKT that can express proteins in high efficacy, and the effect of the DNA vaccine was studied by measuring antibody titers and by a challenge test.
The vector was inserted by CDNA encoding full-size HA gene or headless HA gene, and mice were immunized two times with the DNA vaccine 3 weeks apart by a gene gun. Two weeks after the second immunization, the mice were challenged by A/FM/1/47(H1N1) strain that had been adapted in mouse lung. Control mice immunized with vector only showed significant reduction of body weight and half of them were died. Whereas all the mice immunized with the full-size HA gene were alive without showing loss of body weight. Although 20 % of the mice immunized with headless HA gene were died, the alive mice did not show loss of body weight. When serum antibody in the mice were measured by the neutralization test and ELISA, increase in titers were observed in mice immunized with full-size HA gene but not with headless HA gene. These results seem to indicate that the DNA vaccine with headless HA gene induces cellular immunity more efficiently than humoral immunity.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] N.Nakagawa: "Antigenic variants with amino acid deletions clarify a neutralizing epitope speciflc for influenza B virus Victoria group strains"Journal of General Virology. 82. 2169-2172 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N.Nakagawa: "Characterization of new epidemic strains of influenza B virus by using neutralizing monoclonal antibodies"Journal of Medical Virology. 65. 745-750 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 奥野良信: "高齢者のインフルエンザ予防策"日本医事新報. 4040. 85 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 奥野良信: "インフルエンザの疫学と変異"小児感染免疫. 13. 355-358 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 奥野良信(分担執筆): "感染症研究のいま"大阪大学出版会. 87 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N. Nakagawa: "Antigrnic variaqnts with amino acide deletions clarify a neutralizing epitope specific for influenza B virus Victoria group strain"Journal of General Virology. 82. 2169-2172 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N. Nakagawa: "Characterization of new epidemic strains of influenza B virus by using neutralizing monoclonal antibodies"Journal of Medical Virology. 65. 745-750 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Okuno: "Protective measure against influenza in elderly people (in Japanes)"Japan Medical Journal. 85. 4040 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Okuno: "Epidemiology and viral mutation of influenza (in Japanese)"Infection and Immunity in Childhood. 13. 355-358 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Honda: "Present status of infections disease study (in Japanese)"Osaka University Press. 87 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N.Nakagawa: "Antigenic variants with amino acid deletions clarify a neutralizing epitope specific for influenza B virus Victoria group strains"Journal of General Virology. 82. 2169-2172 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] N.Nakagawa: "Characterization of new epidemic strains of influenza B virus by using neutralizing monoclonal antibodies"Journal of Medical Virology. 65. 745-750 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 奥野良信: "高齢者のインフルエンザ予防策"日本医事新報. 4040. 85 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 奥野良信: "インフルエンザの疫学と変異"小児感染免疫. 13. 355-358 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 奥野良信(分担執筆): "感染症研究のいま"大阪大学出版会. 87 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] N.Nakagawa: "Heterogeneity of influenza B virus strains in one epidemic season differentiated by monoclonal antibodies and nucleotide sequences."Journal of Clinical Microbiology. 38. 3467-3469 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] N.Nakagawa: "Characterization of new epidemic strains of influenza B virus by using neutralizing monoclonal antibodies."Journal of Medical Virology. 61(in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 奥野良信: "インフルエンザワクチンの現況"医学のあゆみ. 192. 1186-1187 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 奥野良信: "新型インフルエンザによる大流行とその対策"Makoto(別冊). 111. 1-7 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 奥野良信: "インフルエンザワクチンの製造と課題"日本胸部臨床. 59. 645-652 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 奥野良信: "最新のインフルエンザウイルス診断法-疫学調査の立場から-"小児科診療. 63. 2089-2092 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 奥野良信: "インフルエンザのすべて-その臨床最前線-"新興医学出版社. 134 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] N. Nakagawa: "Rapid detection and identification of two lineage of influenza B strains with monoclonal antibodies"J. Virol. Methods.. 79. 113-120 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] YA. Smirnov: "A common antigenic epitope in the hemagglutinin of H1, H2, H5 and H6 influenza A viruses"Problems of Virology. 44. 111-115 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] YA. Smirnov: "An epitope shared by the hemagglntinin of H1, H2, H5, and H6 subtypes of influenza A virus"Acta Virologica. 43. 237-244 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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