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新しい概念に基づく自然免疫・獲得免疫両面からの感染防御能の誘導

Research Project

Project/Area Number 19659111
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Bacteriology (including Mycology)
Research InstitutionYokohama City University

Principal Investigator

奥田 研爾  Yokohama City University, 医学研究科, 教授 (40124862)

Co-Investigator(Kenkyū-buntansha) 武下 文彦  横浜市立大学, 医学研究科, 准教授 (60333572)
Project Period (FY) 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2007: ¥3,300,000 (Direct Cost: ¥3,300,000)
Keywords緑膿菌 / TLR5 / 鞭毛抗原 / ワクチン / アジュバント
Research Abstract

フラジェリンは、緑膿菌など多くの細菌の鞭毛タンパクの重要な成分である。フラジェリンはToll like receptor 5(TLR5)を強く活性化し、多くの病原性微生物に対するワクチンのアジュバントとして重要であることが最近分かってきた。我々は、DNAワクチンを主とした緑膿菌ワクチンの検討を行ってきた。緑膿菌のA型(FliA)とB型(FliC)を対にするフラジェリンは、一般的に免疫すると、非常に抗原性が強く、従って、TLR5の活性化部位に対する抗体が出現し、この自然免疫のアジュバント効果も急速に減少することが判明した。そこで、我々は、FliCの90番目のアルギニン(R)をアラニン(A)に1塩基置換したFliC R90Aを作製し、これを免疫することによって、TLR5の活性化が持続的に行われるようになり、アジュバント効果も数十倍上昇することを見出した。しかも、このFliC R90AはD4株、19-106-1株、20-110-1株等の臨床分離株やPAO-1,PAK株等にも感染防御反応を強く発揮することが判明した。このように、フラジェリンの1塩基置換変異体はFliC、あるいはFliAを持つ緑膿菌に対しては、非常に強い防御効果が見られることが分かった。このような考え方は、今までほとんど報告されたことがなかった。我々の実験により、鞭毛を持つ細菌の自然免疫活性化部位を一塩基置換させることにより、自然免疫を中心とする感染防御能がさらに強く発揮できるワクチンが今後多く出現してくるものと思われる。これらの意味で、この自然免疫持続的活性化法の応用的価値は高いと思われる。

Report

(1 results)
  • 2007 Annual Research Report
  • Research Products

    (25 results)

All 2008 2007

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (9 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] TANK-binding kinase-1 delineates innate and adaptive immune respons es to DNA vaccines.2008

    • Author(s)
      Ishii KJ, et. al.
    • Journal Title

      Nature 451

      Pages: 725-730

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The non-canonical role of Atg family members as suppressors of innate antiviral immune signaling.2008

    • Author(s)
      Takeshita F, et. al.
    • Journal Title

      Autophagy 4

      Pages: 1-4

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reliable enzyme-linked immunosorbent assay systems for pathogenic factoys of pseudomonas aeruginosa alkaline proteinase, elastase, and exotoxin A: A comparison of method for labeling detection antibodies with horseradish peroxidase.2007

    • Author(s)
      Shigematsu T, et. al.
    • Journal Title

      Microbilo Immunol 51(12)

      Pages: 1149-1159

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of coxsackie and adenovirus receptor reduces the lung metastatic potential of marine tumor cells.2007

    • Author(s)
      Yamashita M, et. al.
    • Journal Title

      International Journal of cancer 121

      Pages: 1690-1696

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TLR9 expression and function is abolished by the cervical cancer-associated human papillomavirus type 16.2007

    • Author(s)
      Hasan UA al.
    • Journal Title

      J Immunol 178

      Pages: 3186-3197

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutant influenza A virus nucleoprotein is preferentially localized in the cytoplasm and its immunization in mice shows higher immunogenicity and cross-reactivity.2007

    • Author(s)
      Ohba K, et. al.
    • Journal Title

      Vaccine 25

      Pages: 4291-4300

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Age5-Age12 Conjugate associates with innate anti viral immune responses.2007

    • Author(s)
      Jounai N, et. al.
    • Journal Title

      Pro Nat Acad Sci 104(35)

      Pages: 14050-14055

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chimeric adenovirus type 5/35 vector encoding SIV gag and HIV env genes affords protective immunity against the simian/human immunodeficiency virus in monkeys.2007

    • Author(s)
      Someya K, et. al.
    • Journal Title

      Virology 367(11)

      Pages: 390-397

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blocking of the TLR5 activation domain hampers protective potential of DNA vaccine targeting flagellin.2007

    • Author(s)
      Saha S, et. al.
    • Journal Title

      J Immunol 179(2)

      Pages: 1147-1154

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chimeric adenovirus 5/35 vector containing the clade C HIV gag gene induces a cross-reactive immune response against HIV.2007

    • Author(s)
      Xin KQ, et. al.
    • Journal Title

      Vaccine 25(19)

      Pages: 3809-3815

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Muscle creative kinase/SV40 hybrid promoter for muscle-targeted long-term transgene expression.2007

    • Author(s)
      Takeshita F, et. al.
    • Journal Title

      Int J Mol Med 19(2)

      Pages: 309-315

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation and identification of adenovirus from conjunctival scrapings over a two-year period(between 2001-2003)in Yokohama, Japan.2007

    • Author(s)
      Matsui K, et. al.
    • Journal Title

      J Med Virol 79(2)

      Pages: 200-205

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The degree of apoptosis as an immunostimulant for a DNA vaccine against HIV-1 infection.2007

    • Author(s)
      Kojima Y, et. al.
    • Journal Title

      Vaccine 25(3)

      Pages: 438-445

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The synaptic scaffolding protein Delphinline interacts with monocarboxylate transporter 2.2007

    • Author(s)
      Watanabe K, et. al.
    • Journal Title

      NeuroReport 18

      Pages: 489-493

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] デノウイルスベクターにおける中和抗体エスケープ法の確立2008

    • Author(s)
      吉崎慎二、松井清彦、島田勝、奥田研爾
    • Organizer
      第6回感染症沖縄フォーラム
    • Place of Presentation
      沖縄
    • Related Report
      2007 Annual Research Report
  • [Presentation] コアヒストンを介する細胞内異常DNA認識機構2007

    • Author(s)
      武下文彦, 小檜山康司, 鈴木幸一
    • Organizer
      BMB2007
    • Place of Presentation
      神奈川
    • Related Report
      2007 Annual Research Report
  • [Presentation] サルでのウイルスベクターワクチンを用いた治療効果の検討2007

    • Author(s)
      島田勝, 井野麻美, 吉田篤司, 奥田研爾
    • Organizer
      第21回日本エイズ学会
    • Place of Presentation
      広島
    • Related Report
      2007 Annual Research Report
  • [Presentation] development of HIV vaccine induced neutralization antibody by recombinant adenovirus vector2007

    • Author(s)
      浦剛博, 吉田篤司, 吉崎慎二, 奥田研爾
    • Organizer
      第37回日本免疫学会総会・学術集会
    • Place of Presentation
      品川
    • Related Report
      2007 Annual Research Report
  • [Presentation] Analysis of PD-1 expression of HIV-specific T cells induced by HIVenv-containing adenovirus vector2007

    • Author(s)
      吉崎慎二, 浦剛博, 吉田篤司, 奥田研爾
    • Organizer
      第37回日本免疫学会総会・学術集会
    • Place of Presentation
      品川
    • Related Report
      2007 Annual Research Report
  • [Presentation] アデノウイルスベクターにおける中和抗体エスケープ法の確立2007

    • Author(s)
      吉碕慎二, 松井清彦, 島田勝, 奥田研爾
    • Organizer
      第55回日本ウイルス学会学術集会
    • Place of Presentation
      北海道
    • Related Report
      2007 Annual Research Report
  • [Presentation] The Atg5-Atg12 conjugate associates with innate antiviral immune responses2007

    • Author(s)
      Jounai N, Takeshita F, Kobiyama K, Huang J, Suzuki K
    • Organizer
      THE 20TH NAITO CONFERENCE ON Innate Immunity in Medicine and Biology[III]
    • Place of Presentation
      神奈川
    • Related Report
      2007 Annual Research Report
  • [Presentation] istone H2B mediates intracellular recognition of naked DNA and production of type I interferons2007

    • Author(s)
      Kobiyama K, Takeshita F, Jounai N, Okuda K, Ishii KJ, Suzuki K
    • Organizer
      THE 20TH NAITO CONFERENCE ON Innate Immunity in Medicine and Biology[III]
    • Place of Presentation
      神奈川
    • Related Report
      2007 Annual Research Report
  • [Presentation] Blocking of the TLR5 activation domain hampers protective potential of DNA vaccine targeting flagellin2007

    • Author(s)
      Takeshita F, Saha S, Kobiyama K, Jounai N, Okuda K
    • Organizer
      THE 20TH NAITO CONFERENCE ON Innate Immunity in Medicine and Biology[III]
    • Place of Presentation
      神奈川
    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] アルツハイマー病における次世代遺伝子治療法・免疫治療法の開発2008

    • Inventor(s)
      島田勝、奥田研爾
    • Industrial Property Rights Holder
      公立大学法人横浜市立大学
    • Industrial Property Number
      2008-012393
    • Filing Date
      2008-01-23
    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] モノクローナル抗体の作製方法及びそれにより作製されたHIV-1中和モノクローナル抗体2007

    • Inventor(s)
      奥田研爾、吉田篤司、島田勝、浦剛博
    • Industrial Property Rights Holder
      公立大学法人横浜市立大学
    • Industrial Property Number
      2007-283556
    • Filing Date
      2007-10-31
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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