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Studies on the efficacy of toxin neutralization and safety of Shiga toxin-specific secretory IgA type plantibody produced by practical plants

Research Project

Project/Area Number 15H04660
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental and hygienic pharmacy
Research InstitutionUniversity of Shizuoka

Principal Investigator

Imai Yasuyuki  静岡県立大学, 薬学部, 教授 (80160034)

Co-Investigator(Kenkyū-buntansha) 黒羽子 孝太  静岡県立大学, 薬学部, 講師 (90333525)
Co-Investigator(Renkei-kenkyūsha) Kobayashi Hirokazu  静岡県立大学, 大学院 食品栄養環境科学研究院, 教授 (80170348)
Niwa Yasuo  静岡県立大学, 大学院 食品栄養環境科学研究院, 助教 (00222191)
Research Collaborator NAKANISHI Katsuhiro  
AKIMOTO Yoshihiro  
KAWAKAMI Hayato  
MATSUBARA Sachie  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywords抗体医薬 / 植物発現系 / 粘膜免疫 / 免疫グロブリンA / 微生物
Outline of Final Research Achievements

Transgenic plants that produce secretory immunoglobulin A (SIgA) specific to Shiga toxin 1 (Stx1) were developed using a model plant (Arabidopsis thaliana) and a vegetable (Lactuca sativa). Considering the initial entry of Stx1 can occur through cytotoxicity to colon epithelial cells, we established an assay using a human colon cell line, Caco-2. Plant-made IgA neutralized the toxicity of Stx1 against Caco-2 cells. Production of secretory component (SC), a component of SIgA, was increased in the transgenic plants by the addition of an endoplasmic reticulum retention signal to SC. When plant-made SC was administered to mice, anti-SC antibodies were induced by intravenous administration while no such antibodies were made by oral administration. This result provides evidence as to the safety of oral application of plant-made biologics.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (19 results)

All 2018 2017 2016 2015 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) Remarks (5 results)

  • [Journal Article] Protection of human colon cells from Shiga toxin by plant-based recombinant secretory IgA2017

    • Author(s)
      Katsuhiro Nakanishi, Shota Morikane, Shiori Ichikawa, Kohta Kurohane, Yasuo Niwa, Yoshihiro Akimoto, Sachie Matsubara, Hayato Kawakami, Hirokazu Kobayashi, Yasuyuki Imai
    • Journal Title

      Sci. Rep.

      Volume: 7 Issue: 1 Pages: 45843-45843

    • DOI

      10.1038/srep45843

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 1型線毛に結合するIgA型イムノアドヘシンの作製2018

    • Author(s)
      中西勝宏、黒羽子孝太、今井康之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 植物由来組換え型分泌片を活用した抗原特異的分泌型IgAの構築と消化酵素抵抗性の付与2018

    • Author(s)
      菊地祐希、松田弥奈美、森兼捷太、中西勝宏、黒羽子孝太、丹羽康夫、小林裕和、今井康之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 分泌型ハイブリッドIgA植物抗体によるベロ毒素のヒト腸管上皮細胞に対する細胞毒性の中和効果の検討2017

    • Author(s)
      中西勝宏、黒羽子孝太、丹羽康夫、小林裕和、今井康之
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 植物で作製した分泌片を活用した分泌型IgAの消化酵素抵抗性に関する研究2017

    • Author(s)
      松田弥奈美、森兼捷太、中西勝宏、黒羽子孝太、丹羽康夫、小林裕和、今井康之
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 植物で作製した小胞体保留シグナル付加分泌片の糖鎖解析2017

    • Author(s)
      梶原優佳、森兼捷太、中西勝宏、黒羽子孝太、丹羽康夫、小林裕和、今井康之
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] Production of secretory hybrid-IgG/IgA in plant expression system.2017

    • Author(s)
      Katsuhiro Nakanishi, Kohta Kurohane, Yasuyuki Imai
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Establishment of secretory hybrid IgA with binding to Shiga toxin 1 binding subunit in lettuce2016

    • Author(s)
      Katsuhiro Nakanishi, Kohta Kurohane, Yasuo Niwa, Hirokazu Kobayashi, Yasuyuki Imai
    • Organizer
      第21回静岡健康・長寿学術フォーラム
    • Place of Presentation
      静岡
    • Year and Date
      2016-11-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] ベロ毒素に対する分泌型ハイブリッドIgAの植物での産生と細胞内局在の解析2016

    • Author(s)
      中西勝宏、黒羽子孝太、丹羽康夫、松原幸枝、秋元義弘、川上速人、小林裕和、今井康之
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] 小胞体保留シグナルを利用した分泌型IgAの植物での生産性向上2016

    • Author(s)
      森兼捷太、細川奈緒、中西勝宏、黒羽子孝太、丹羽康夫、小林裕和、今井康之
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] Intrarectal administration of Shiga toxin 1 injures mouse colonic epithelial cells2015

    • Author(s)
      Katsuhiro Nakanishi, Kohta Kurohane, Yasuyuki Imai
    • Organizer
      第44回日本免疫学会
    • Place of Presentation
      札幌
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Production of secretory component-KDEL in Arabidopsis thaliana2015

    • Author(s)
      Nao Hosokawa, Katsuhiro Nakanishi, Kohta Kurohane, Yasuyuki Imai
    • Organizer
      第44回日本免疫学会
    • Place of Presentation
      札幌
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] 機能解析を目指した植物発現hybrid IgA抗体の精製2015

    • Author(s)
      杉野嵩朋、中西勝宏、鶴田昌吾、黒羽子孝太、丹羽康夫、小林裕和、今井康之
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部 合同学術大会2015
    • Place of Presentation
      名古屋
    • Year and Date
      2015-11-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Hybrid IgA expressed in Arabidopsis is localized in the protein body-like structure in the leaves2015

    • Author(s)
      Katsuhiro Nakanishi, Kohta Kurohane, Sachie Matsubara, Yoshihiro Akimoto, Hayato Kawakami, Yasuo Niwa, Hirokazu Kobayashi, Yasuyuki Imai
    • Organizer
      植物電子顕微鏡ワークショップ2015
    • Place of Presentation
      横浜
    • Year and Date
      2015-09-25
    • Related Report
      2015 Annual Research Report
  • [Remarks] 静岡県立大学薬学部免疫微生物学教室のホームページ

    • URL

      http://w3pharm.u-shizuoka-ken.ac.jp/bisei/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 静岡県立大学薬学部免疫微生物学教室のホームページ(英語)

    • URL

      http://w3pharm.u-shizuoka-ken.ac.jp/bisei/English/index.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 免疫微生物学教室のホームページ

    • URL

      http://w3pharm.u-shizuoka-ken.ac.jp/bisei/

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
  • [Remarks] 免疫微生物学教室のホームページ(英語)

    • URL

      http://w3pharm.u-shizuoka-ken.ac.jp/bisei/English/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 免疫微生物学教室のホームページ(英語)

    • URL

      http://w3pharm.u-shizuoka-ken.ac.jp/bisei/English/index.html

    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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