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Development of a new immunostimulatory drug for non-haemolytic alternative to PQ.

Research Project

Project/Area Number 18K19394
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 47:Pharmaceutical sciences and related fields
Research InstitutionKanazawa University

Principal Investigator

YOSHIDA Shigeto  金沢大学, 薬学系, 教授 (10296121)

Co-Investigator(Kenkyū-buntansha) 伊従 光洋  金沢大学, 薬学系, 准教授 (20608351)
Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords三日熱マラリア / プリマキン / 自然免疫 / バキュロウルス / マラリア / バキュロウイルス / インターフェロン / ヒプノゾイト
Outline of Final Research Achievements

Baculovirus (BV)-induced innate immunity completely kills liver-stage parasites using IFN-aRKO and IFN-gRKO mice. As primaquine (PQ) is the only licensed drug for the radical cure of P. vivax hypnozoites, we compared the elimination effects of BV with those of PQ. Treatment with PQ could not exclude liver-stage parasites. Treatment with BV proves to be more effective than PQ. BV effectively induces fast-acting innate immune responses that provide powerful first lines of both defensive and offensive attacks against pre-erythrocytic parasites. Our results illustrate the potential of BV as a new potent prophylactic and therapeutic immunostimulatory agent against pre-erythrocytic stage parasites.

Academic Significance and Societal Importance of the Research Achievements

三日熱マラリアの根治治療に使用されている唯一の薬プリマキンは、多くの禁忌、副作用があり三日熱マラリアコントロールの障害となっている。BVが誘導する自然免疫応答が肝臓期マラリア原虫に対して強力な殺傷効果を発揮するメカニズムを一部解明できたことは、BVを利用したプリマキンに替わる新しいコンセプトの抗マラリア新薬の開発につながる。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (38 results)

All 2020 2019 2018 Other

All Int'l Joint Research (4 results) Journal Article (6 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (24 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results) Patent(Industrial Property Rights) (4 results)

  • [Int'l Joint Research] University of Cambridge(英国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Universidade Nove de Lisboa(ポルトガル)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Oxford/Imperial College Lodon(英国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Universidade Nova de Lisboa(ポルトガル)

    • Related Report
      2018 Research-status Report
  • [Journal Article] A Viral-Vectored Multi-Stage Malaria Vaccine Regimen With Protective and Transmission-Blocking Efficacies2019

    • Author(s)
      Yusuf Y, Yoshii T, Iyori M, Mizukami H, Fukumoto S, Yamamoto DS, Emran TB, Amelia F, Islam A, Syafira I, Yoshida S.
    • Journal Title

      Front Immunol

      Volume: 10 Pages: 2412-2412

    • DOI

      10.3389/fimmu.2019.02412

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Adeno-Associated Virus as an Effective Malaria Booster Vaccine Following Adenovirus Priming2019

    • Author(s)
      Yusuf Y, Yoshii T, Iyori M, Yoshida K, Mizukami H, Fukumoto S, Yamamoto DS, Alam A, Emran TB, Amelia F, Islam A, Otsuka H, Takashima E, Tsuboi T, Yoshida S.
    • Journal Title

      Frontiers in Immunology

      Volume: 10 Pages: 730-730

    • DOI

      10.3389/fimmu.2019.00730

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anopheline antiplatelet protein from mosquito saliva regulates blood feeding behavior.2019

    • Author(s)
      Islam A, Emran TB, Yamamoto DS, Iyori M, Amelia F, Yusuf Y, Yamaguchi R, Alam MS, Silveira H, Yoshida S.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 3129-3129

    • DOI

      10.1038/s41598-019-39960-2

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Down‐selecting circumsporozoite protein‐based malaria vaccine: a comparison of malaria sporozoite challenge model2019

    • Author(s)
      Amelia F, Iyori M, Emran TB, Yamamoto DS, Genshi K, Otsuka H, One Y, Yusuf Y, Islam A, Yoshida S.
    • Journal Title

      Parasite Immunology

      Volume: 1 Issue: 5 Pages: 1-1

    • DOI

      10.1111/pim.12624

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Adenovirus-prime and baculovirus-boost heterologous immunization achieves sterile protection against malaria sporozoite challenge in a murine model.2018

    • Author(s)
      Yoshida K, Iyori M, Blagborough AM, Salman AM, Dulal P, Sala KA, Yamamoto DS, Khan SM, Janse CJ, Biswas S, Yoshii T, Yusuf Y, Tokoro M, Hill AVS, Yoshida S
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 3896-3896

    • DOI

      10.1038/s41598-018-21369-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Baculovirus-Induced Fast-Acting Innate Immunity Kills Liver-Stage Plasmodium.2018

    • Author(s)
      Emran TB, Iyori M, Ono Y, Amelia F, Yusuf Y, Islam A, Alam A, Tamura M, Ogawa R, Matsuoka H, Yamaoto DS, Yoshida S.
    • Journal Title

      The Journal of Immunology

      Volume: 201 Issue: 8 Pages: 2441-2441

    • DOI

      10.4049/jimmunol.1800908

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] A viral-vectored multi-stage malaria vaccine regimen with protective and transmission-blocking efficacies2020

    • Author(s)
      吉田栄人
    • Organizer
      4th Global Conference and Expo on Vaccines Research & Development
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The mechanism of PfCSP-based malaria vaccines and its application to the viral vectored vaccine platform2019

    • Author(s)
      Iyori M、Amelia F、Yusuf Y、Yamamoto DS、Fukumoto S、Yoshida K、Genshi K、Yoshii T、 Mizukami H、Yoshida S
    • Organizer
      17th International Congress of Immunology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Anopheline anti-platelet protein (AAPP), a novel saliva protein, enables blood acquisition in Anopheles stephensi2019

    • Author(s)
      Islam A、 Iyori M、Yamamoto DS、Tuno N、 Yamaguchi R、Silveira H、 Yoshida S
    • Organizer
      第75回日本寄生虫学会西日本支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] バキュロウイルス筋肉内接種による肝臓期マラリア原虫の殺傷と遺伝子発現解析2019

    • Author(s)
      伊從光洋、小川 良平、新倉 保、Talha Bin Emran、丹保 秀太、井上 信一、小林富美惠、吉田栄人
    • Organizer
      第75回日本寄生虫学会西日本支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ウイルスベクターと組換えタンパクを用いたPfCSP マラリアワクチンによる免疫応答の多様性2019

    • Author(s)
      大塚 広夢、伊從光洋、吉田 栄人
    • Organizer
      第75回日本寄生虫学会西日本支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Liver-directed AAV8 vaccine expressing PfCSP elicits complete protection against sporozoitechallenge2019

    • Author(s)
      Shahnaij M、Iyori M、Islam A、Syafira I、IYamagoshi I、Kajino M、Yoshida S
    • Organizer
      第75回日本寄生虫学会西日本支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A two-dose multi-stage malaria vaccine regimen elicits protection and blocks parasite transmission2019

    • Author(s)
      Yusuf Y、Yoshii T、Iyori M、Mizukami H、Yoshida S
    • Organizer
      第75回日本寄生虫学会西日本支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肝臓期マラリア原虫をバキュロウイルス投与で治療した後に誘導される獲得免疫応答の解析2019

    • Author(s)
      井谷慧、伊從光洋、辻村聡恵、吉田栄人
    • Organizer
      第75回日本寄生虫学会西日本支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Full-length Plasmodium falciparum circumsporozoite protein administrated with Imject Alum elicits complete protection in mice against the transgenic P. berghei sporozoites2019

    • Author(s)
      Iyori M、Amelia F、Genshi K、Onoue Y、Emran TB、 Yoshida S
    • Organizer
      PROTEIN ISLAND MATSUYAMA 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ウイルスベクタープラットフォームを基盤とした乳児用次世代型マラリアワクチン2019

    • Author(s)
      吉田栄人
    • Organizer
      日本薬学会第139年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] アデノ随伴ウイルスをもとにした長期間強力な効果が持続する伝播阻止マラリアワクチン2019

    • Author(s)
      吉井達也、Yenni Y、伊從光洋、水上浩明、坪井敬文、高島英造、吉田 栄人
    • Organizer
      第88回日本寄生虫学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The impact of baculovirus-induced innate immunity on elimination of the liver-stage Plasmodium through interferon signaling2019

    • Author(s)
      伊從光洋、 Emran TB、小野 祐希、吉田 栄人
    • Organizer
      第88回日本寄生虫学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The impact of baculovirus-induced innate immunity on elimination of the liver-stage Plasmodium through interferon signaling.2019

    • Author(s)
      伊従 光洋, Emran TB, 小野 祐希, 吉田 栄人
    • Organizer
      第88回日本寄生虫学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] ウイルスベクタープラットフォームを基盤とした乳児用次世代型マラリアワクチン2019

    • Author(s)
      吉田 栄人
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] マラリアワクチン開発を基盤とした新規感染用ワクチンプラットフォームの創出―非感染性バキュロウイルスナノ粒子ワクチンスステムの開発研究-2018

    • Author(s)
      伊従 光洋
    • Organizer
      第120回日本小児科学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 唾液タンパクAAPPを欠損したトランスジェニックハマダラカの吸血行動の著しい制約2018

    • Author(s)
      slam A, 伊従 光洋, 山本 大介, Emran TB, 都野 展子, 山口 莉理夏, Amelia F, Yenni Y, Silveira H, 吉田 栄人
    • Organizer
      第70回日本衛生動物学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Baculovirus-induced innate immunity confers complete protection against Plasmodium pre-erythrocytic stage parasites2018

    • Author(s)
      Emran TB, Iyori M, Yoshida S
    • Organizer
      14th International congress of parasitology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of a novel malaria vaccine based on heterologous prime-boost immunization regimen using adenovirus and adeno-associated virus vectors2018

    • Author(s)
      Iyori M, Yoshida K, Yusuf Y, Emran TB, Yoshii T, Hashizume H, Shimada S, Yamamoto DS, Fukumoto S, Mizukami H, Yoshida S
    • Organizer
      14th International congress of parasitology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 肝臓期マラリア原虫を完全排除可能な非感染性ウイルスベクターに関する研究2018

    • Author(s)
      伊従 光洋, Emran TB, 小野 祐希, 松岡 裕之, 山本 大介, 吉田 栄人
    • Organizer
      第74回日本寄生虫学会西日本支部大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 組換えワクシニアウイルスLC16m8Δを基盤としたマラリアワクチンの感染防御効果の検討 (II)2018

    • Author(s)
      山越 彩葉, 伊従 光洋, 堀 直人, Emran TB, 志田 壽利, 吉田 栄人.
    • Organizer
      第74回日本寄生虫学会西日本支部大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 感染症媒介蚊由来唾液タンパクの種間比較2018

    • Author(s)
      山下 陽夏, 伊従 光洋, 山口 莉理夏, Isram A, 吉井 達也, 吉田 栄人
    • Organizer
      第74回日本寄生虫学会西日本支部大会
    • Related Report
      2018 Research-status Report
  • [Presentation] バキュロウイルス投与による肝臓期マラリア原虫の殺傷メカニズムに関する研究2018

    • Author(s)
      小野 祐希, 伊従 光洋, Emran TB, 田村 めぐみ, 尾上 裕太郎, 小川 良平, 吉田 栄人
    • Organizer
      第74回日本寄生虫学会西日本支部大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 組換えワクシニアウイルスLC16m8Δのマラリアワクチンとしての新規アプローチ2018

    • Author(s)
      堀 直人, 伊従 光洋, 吉田 邦嵩, Emran TB, 島田 聡, Islam A, 志田 壽利, 吉田 栄人
    • Organizer
      第74回日本寄生虫学会西日本支部大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 強力な抗肝臓期マラリア原虫効果を発揮する自然免疫応答2018

    • Author(s)
      辻村 聡恵, 伊従 光洋, Emran TB, 吉井 達也, 吉田 栄人
    • Organizer
      第74回日本寄生虫学会西日本支部大会
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] マラリアワクチン2019

    • Inventor(s)
      吉田 栄人、水上 浩明、伊從 光洋
    • Industrial Property Rights Holder
      吉田 栄人、水上 浩明、伊從 光洋
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-207373
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 組換えアデノ随伴ウイルスを含むマラリアワクチン2019

    • Inventor(s)
      吉田 栄人、水上 浩明、伊従 光洋、吉井 達也
    • Industrial Property Rights Holder
      国立大学法人金沢大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-019247
    • Filing Date
      2019
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] マラリアワクチン2018

    • Inventor(s)
      吉田 栄人、志田 壽利、伊従 光洋、堀 直人、吉田 邦嵩
    • Industrial Property Rights Holder
      国立大学法人金沢大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-038100
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] マラリア治療剤、マラリア予防剤及び抗マラリア自然免疫賦活剤2018

    • Inventor(s)
      吉田 栄人
    • Industrial Property Rights Holder
      国立大学法人金沢大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-057311
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2021-02-19  

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