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Development of a hemin-containing copolymer as a novel immunostimulator

Research Project

Project/Area Number 15K06589
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biofunction/Bioprocess
Research InstitutionNational Institute for Materials Science

Principal Investigator

YAMAZAKI TOMOHIKO  国立研究開発法人物質・材料研究機構, 機能性材料研究拠点, 主幹研究員 (50419264)

Co-Investigator(Kenkyū-buntansha) 吉川 千晶  国立研究開発法人物質・材料研究機構, 国際ナノアーキテクトニクス研究拠点, 主任研究員 (10447930)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsヘモゾイン / トール様受容体 / アジュバント / ヘミン / イソプロピルアクリルアミド / インターフェロン / インターロイキン / 末梢血単核球細胞 / アジュバンド / インフラマソーム / インターフェロンγ / 免疫活性化 / トール様受容体9 / 相互作用 / 末梢血単核細胞
Outline of Final Research Achievements

Toll-like receptor 9 (TLR9) plays an important role in the production of cytokines and expression of co-stimulatory molecules necessary for the activation of immunity. TLR9 agonists have attracted much attention for the development of vaccine adjuvants or therapeutic reagents for cancer and allergies.
Hemozoin, a biocrystal synthesized by the Plasmodium parasite, is responsible for the induction of a strong inflammatory response mediated by TLR9 activation. We focused on the heme-repeated structure on the hemozoin surface, we synthesized a novel hemozoin mimicking polymer and evaluated its stimulatory effects in vitro. In human immune cells, the hemozoin-mimicking polymer induced the production of large amounts of interferon gamma, which is the major molecule involved in the differentiation of T helper cells to Th1 cells. Therefore, the polymer shows potential as a new adjuvant.

Academic Significance and Societal Importance of the Research Achievements

本研究では、ヘモゾインのヘム繰り返し構造に着目し、新規ヘム含有免疫活性化剤を開発した。開発した分子は抗体産出を誘導する水溶性分子であることから、ワクチン添加剤としての扱いが容易である。核酸をベースとした既存アジュバントと比較して安定性が高く、また粒子をベースとした既存アジュバンドと比較して炎症の誘発が低いことから、安全かつ効果の高いアジュバンド分子であり、今後ワクチンへの応用が期待される。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (26 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (4 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (13 results) (of which Int'l Joint Research: 7 results,  Invited: 4 results) Remarks (6 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] Lund university(スウェーデン)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] The University of North carolina(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Pure and Applied Biochemistry/Lund university(スウェーデン)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Pure and Applied Biochemistry/Lund university(スウェーデン)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Synthesis of a hemin-containing copolymer as a novel immunostimulator that induces IFN-gamma production2018

    • Author(s)
      Hoshi Kazuaki、Yamazaki Tomohiko、Yoshikawa Chiaki、Tsugawa Wakako、Ikebukuro Kazunori、Sode Koji
    • Journal Title

      International Journal of Nanomedicine

      Volume: Volume 13 Pages: 4461-4472

    • DOI

      10.2147/ijn.s166259

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Development of novel immunostimulatory ligands of toll like receptor 9, as potent activators of the innate immune system2018

    • Author(s)
      Tomohiko YAMAZAKI
    • Organizer
      6th Annual Meeting of Hypoxia and Oxidative Stress Studies
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of novel immunostimulatory ligands of Toll-like receptor 9 as potent activators of the innate immune system2018

    • Author(s)
      Tomohiko YAMAZAKI
    • Organizer
      Second Interdisciplinary and Research Alumni Symposium iJaDe2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of a polymer based immunostimulatory ligand mimicking malarial hemozoin2018

    • Author(s)
      Tomohiko YAMAZAKI
    • Organizer
      CSIRO-NIMS symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 免疫活性化能を有するヘミン含有ポリマーの開発2018

    • Author(s)
      星和明、津川若子、早出広司、池袋一典、山崎智彦
    • Organizer
      第27回インテリジェント材料・システムシンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] ヘミン含有免疫活性化剤の開発2017

    • Author(s)
      星和明、山崎智彦、津川若子、早出広司
    • Organizer
      第11回バイオ関連化学シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] Gカルテット構造形成によるCpG ODNの免疫活性能の向上2017

    • Author(s)
      山崎智彦、星和明、杉山雄紀、塚越かおり、津川若子、早出広司、池袋一典
    • Organizer
      第69回日本生物工学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 構造制御による免疫活性化CpG ODNの機能向上2017

    • Author(s)
      山崎智彦
    • Organizer
      つくば医工連携フォーラム 2017
    • Place of Presentation
      千現地区、物質・材料研究機構, つくば
    • Related Report
      2016 Research-status Report
  • [Presentation] Improved immunostimulatory activity of phosphodiester CpG oligodeoxynucleotides by G-quadruplex formation2016

    • Author(s)
      山崎智彦、花方信孝
    • Organizer
      International Symposium on Nanomedicine
    • Place of Presentation
      つくば中央、産業技術総合研究所、つくば
    • Year and Date
      2016-11-24
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Increased immunostimulatory activity of CpG ODNs by G-quadruplex structures2016

    • Author(s)
      星和明、塚越かおり、早出広司、津川若子、池袋一典
    • Organizer
      2nd International Symposium on Nanoarchitectonics for Mechanobio
    • Place of Presentation
      並木地区、物質・材料研究機構, つくば
    • Year and Date
      2016-07-27
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] DNA structure control immunostimulatory effect of CpG ODN2016

    • Author(s)
      K. Hoshi, K. Sode, W. Tsugawa, K. Ikebukuro, N. Hanagata, Tomohiko Yamazaki
    • Organizer
      MANA International Symposium 2016
    • Place of Presentation
      つくば国際会議場、つくば市
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 免疫活性化DNAナノ構造体2016

    • Author(s)
      星和明、山崎智彦
    • Organizer
      つくば医工連携フォーラム2016
    • Place of Presentation
      産業技術総合研究所つくばセンター、つくば市
    • Year and Date
      2016-01-22
    • Related Report
      2015 Research-status Report
  • [Presentation] CpGオリゴヌクレオチドの免疫活性能に対するポリグアノシンの影響2015

    • Author(s)
      山崎智彦、花方信孝
    • Organizer
      第67回日本生物工学会大会
    • Place of Presentation
      城山観光ホテル、鹿児島市
    • Year and Date
      2015-10-26
    • Related Report
      2015 Research-status Report
  • [Presentation] Recognition of CpG olygodeoxynucleotides by human Toll-like receptor 92015

    • Author(s)
      T. YAMAZAKI, S. SUWARTI, N. HANAGATA
    • Organizer
      Toll 2015
    • Place of Presentation
      Palacio de Congresos de Mabella, Marbella, Spain
    • Year and Date
      2015-09-30
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Remarks] 研究者総覧「SAMURAI」

    • URL

      https://samurai.nims.go.jp/profiles/YAMAZAKI_Tomohiko?locale=ja

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Remarks] ナノメディシングループ ホームページ

    • URL

      https://www.nims.go.jp/group/nanomedicine/

    • Related Report
      2018 Annual Research Report
  • [Remarks] ナノメディシングループ ホームページ

    • URL

      http://www.nims.go.jp/group/nanomedicine/

    • Related Report
      2017 Research-status Report 2016 Research-status Report
  • [Remarks] 研究者情報データベース「SAMURAI」

    • URL

      http://samurai.nims.go.jp/YAMAZAKI_Tomohiko-j.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 研究者データーベース

    • URL

      http://samurai.nims.go.jp/YAMAZAKI_Tomohiko-j.html

    • Related Report
      2015 Research-status Report
  • [Remarks] グループホームページ

    • URL

      http://www.nims.go.jp/bmc/group/control/GBSCUM/index.html

    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] 共重合体、免疫アジュバントおよび非ヒト動物を免疫する方法2018

    • Inventor(s)
      山崎智彦、吉川千晶、星和明
    • Industrial Property Rights Holder
      国立研究開発機構物質・材料研究機構
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-112204
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] ヘム骨格を有するポリマーアジュバント2017

    • Inventor(s)
      山崎智彦、吉川千晶、星和明
    • Industrial Property Rights Holder
      国立研究開発法人物質・材料研究機構
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-171231
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report

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Published: 2015-04-16   Modified: 2021-03-11  

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