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Screening for novel transmission-blocking vaccine targets from plasma of patients infected with Plasmodium vivax

Research Project

Project/Area Number 19KK0206
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionTokyo Medical and Dental University (2021-2023)
Ehime University (2019-2020)

Principal Investigator

ISHINO TOMOKO  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (40402680)

Co-Investigator(Kenkyū-buntansha) 橘 真由美  愛媛大学, プロテオサイエンスセンター, 助教 (00301325)
馬場 みなみ  愛媛大学, プロテオサイエンスセンター, 研究員 (00814906)
鳥居 本美  愛媛大学, プロテオサイエンスセンター, 客員研究員 (20164072)
入子 英幸  神戸大学, 保健学研究科, 准教授 (60346674)
Project Period (FY) 2019-10-07 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2020: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords三日熱マラリア / タイ王国 / 伝搬阻止ワクチン / 三日熱マラリア原虫 / 有性生殖 / 生殖体 / マラリア原虫 / 伝搬阻止法
Outline of Research at the Start

主にアジアで流行する三日熱マラリアは、致死性の低さおよび原虫の入手が困難なことから、経済/保健衛生における影響の大きさにも関わらず対策が遅れている。媒介蚊の体内でマラリア原虫の発育を止める伝搬阻止ワクチンの開発が期待されているが、未だ実用化に至っていない。本研究は、流行地の住人の血漿に伝搬阻止効果が認められることに着目し、自然感染により獲得された伝搬阻止抗体が、どの原虫タンパク質によって誘導されたかを明らかにすることで、有効なワクチン抗原を探索することを目的とし、タイ王国の研究者と協力して遂行する。

Outline of Final Research Achievements

Plasmodium vivax malaria has been neglected due to its less lethality and difficulty in obtaining parasites. The development of transmission-blocking vaccines is highly anticipated, but the low immunogenicity of candidate antigens has hindered practical application. This study aims to identify target antigens by selecting IgG antibodies with transmission-blocking effects from patients in endemic regions acquired through natural infection.

In collaboration with researchers from Thailand, we obtained valuable materials, including infected red blood cells and plasma from patients with Plasmodium vivax. Among the sera from 37 patients, 22 contained antibodies with transmission-blocking effects. The low correlation between the levels of known transmission-blocking antibodies and their inhibitory effects suggests the presence of novel vaccine targets.

Academic Significance and Societal Importance of the Research Achievements

熱帯熱マラリア原虫のスポロゾイトを標的とする感染阻止ワクチンが2021年にWHOに使用が推奨された。一方で、アジアで主に流行する三日熱マラリア原虫については、未だ有効な予防法が開発されていない。三日熱マラリアは致死性が低いため、患者が屋内に留まらないことも感染流行の抑制を困難にする要因である。蚊による伝搬のステップを標的にする伝搬阻止ワクチンは、三日熱マラリア対策に効果的と期待される。本研究により、患者が自然感染により獲得した抗体の中に強い伝搬阻止効果が認められ、既知の抗原と異なることが見出された。今後標的分子を同定することでヒト体内で誘導されやすい伝搬阻止ワクチンの開発へ展開できる。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (29 results)

All 2024 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (5 results) Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (12 results) (of which Int'l Joint Research: 8 results,  Invited: 5 results) Remarks (4 results)

  • [Int'l Joint Research] マヒドン大学(タイ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] ペンシルバニア大学/アメリカ国立衛生研究所(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] マヒドン大学(タイ)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Mahidol University(タイ)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] マヒドン大学(タイ)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Identification of a novel protein localized to the crystalloid of the Plasmodium ookinete2024

    • Author(s)
      Tachibana Mayumi、Baba Minami、Iriko Hideyuki、Shinzawa Naoaki、Torii Motomi、Ishino Tomoko
    • Journal Title

      Parasitology International

      Volume: 101 Pages: 102892-102892

    • DOI

      10.1016/j.parint.2024.102892

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Naturally Acquired Transmission-Blocking Immunity Against Different Strains of <i>Plasmodium vivax</i> in a Malaria-Endemic Area in Thailand2023

    • Author(s)
      Thongpoon Sataporn、Roobsoong Wanlapa、Nguitragool Wang、Chotirat Sadudee、Tsuboi Takafumi、Takashima Eizo、Cui Liwang、Ishino Tomoko、Tachibana Mayumi、Miura Kazutoyo、Sattabongkot Jetsumon
    • Journal Title

      The Journal of Infectious Diseases

      Volume: 229 Issue: 2 Pages: 567-575

    • DOI

      10.1093/infdis/jiad469

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Pvs25 mRNA vaccine induces complete and durable transmission-blocking immunity to Plasmodium vivax2023

    • Author(s)
      Kunkeaw Nawapol、Nguitragool Wang、Takashima Eizo、Kangwanrangsan Niwat、Muramatsu Hiromi、Tachibana Mayumi、Ishino Tomoko、Lin Paulo J. C.、Tam Ying K.、Pichyangkul Sathit、Tsuboi Takafumi、Pardi Norbert、Sattabongkot Jetsumon
    • Journal Title

      npj Vaccines

      Volume: 8 Issue: 1 Pages: 187-187

    • DOI

      10.1038/s41541-023-00786-9

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Plasmodium vivax transmission-blocking vaccines: Progress, challenges and innovation2022

    • Author(s)
      Tachibana Mayumi、Takashima Eizo、Morita Masayuki、Sattabongkot Jetsumon、Ishino Tomoko、Culleton Richard、Torii Motomi、Tsuboi Takafumi
    • Journal Title

      Parasitology International

      Volume: 87 Pages: 102525-102525

    • DOI

      10.1016/j.parint.2021.102525

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vaccine co-display of CSP and Pfs230 on liposomes targeting two Plasmodium falciparum differentiation stages2022

    • Author(s)
      Huang Wei-Chiao、Mabrouk Moustafa T.、Zhou Luwen、Baba Minami、Tachibana Mayumi、Torii Motomi、Takashima Eizo、Locke Emily、Plieskatt Jordan、King C. Richter、Coelho Camila H.、Duffy Patrick E.、Long Carole、Tsuboi Takafumi、Miura Kazutoyo、Wu Yimin、Ishino Tomoko、Lovell Jonathan F.
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 773-773

    • DOI

      10.1038/s42003-022-03688-z

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PSOP1, putative secreted ookinete protein 1, is localized to the micronemes of Plasmodium yoelii and P. berghei ookinetes2021

    • Author(s)
      Tachibana Mayumi、Iriko Hideyuki、Baba Minami、Torii Motomi、Ishino Tomoko
    • Journal Title

      Parasitology International

      Volume: 84 Pages: 102407-102407

    • DOI

      10.1016/j.parint.2021.102407

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] The C-terminal region of the Plasmodium yoelii microgamete surface antigen PyMiGS induces potent anti-malarial transmission-blocking immunity in mice2020

    • Author(s)
      Tachibana Mayumi、Baba Minami、Takashima Eizo、Tsuboi Takafumi、Torii Motomi、Ishino Tomoko
    • Journal Title

      Vaccine

      Volume: 38 Issue: 15 Pages: 3129-3136

    • DOI

      10.1016/j.vaccine.2020.02.058

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Observation of Morphological Changes of Female Osmiophilic Bodies Prior to Plasmodium Gametocyte Egress From Erythrocytes2020

    • Author(s)
      Ishino T, Tachibana M, Baba M, Iriko H, Tsuboi T, Torii M.
    • Journal Title

      Mol Biochem Parasitol

      Volume: 236 Pages: 111261-111261

    • DOI

      10.1016/j.molbiopara.2020.111261

    • NAID

      120006873067

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] mRNAワクチン技術を用いたPvs25三日熱マラリア伝搬阻止ワクチンの開発2024

    • Author(s)
      Eizo Takashima, Nawapol Kunkeaw, Wang Nguitragool, Niwat Kangwanrangsan, Hiromi Muramatsu, Mayumi Tachibana, Tomoko Ishino, Paulo J. C. Lin, Ying K. Tam, Sathit Pichyangkul, Takafumi Tsuboi, Norbert Pardi, Jetsumon Sattabongkot
    • Organizer
      第93回 日本寄生虫学会大会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PyMiGS on the microgamete surface is involved in fertilization2023

    • Author(s)
      橘真由美、 鳥居本美、 馬場みなみ、 石野智子
    • Organizer
      Protein Island in Matsuyama
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A Pvs25 mRNA vaccine induces complete and durable transmission-blocking immunity to Plasmodium vivax2023

    • Author(s)
      Nawapol Kunkeaw, Wang Nguitragool, Eizo Takashima, Niwat Kangwanrangsan, Hiromi Muramatsu, Mayumi Tachibana, Tomoko Ishino, Paulo J. C. Lin, Ying K. Tam, Sathit Pichyangkul, Takafumi Tsuboi, Norbert Pardi, Jetsumon Sattabongkot
    • Organizer
      US-Japan Cooperative Medical Sciences Program
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of a potent Pvs25 mRNA vaccine to block transmission of Plasmodium vivax2023

    • Author(s)
      Nawapol Kunkeaw, Wang Nguitragool, Eizo Takashima, Niwat Kangwanrangsan, Hiromi Muramatsu, Mayumi Tachibana, Tomoko Ishino, Paulo J. C. Lin, Ying K. Tam, Sathit Pichyangkul, Takafumi Tsuboi, Norbert Pardi, Jetsumon Sattabongkot
    • Organizer
      Protein Island in Matsuyama
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular mechanisms of malaria transmission to mammals via mosquitoes.2022

    • Author(s)
      Tomoko Ishino.
    • Organizer
      The 20th International Congress for Tropical Medicine and Malaria (ICTMM)
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 異なる2つのステージを標的とするマラリアワクチンの開発に向けて2022

    • Author(s)
      Wei-Chiao Huang, Moustafa T Mabrouk, Luwen Zhou, 馬場 みなみ, 橘 真由美, 鳥居 本 美, 高島 英造, Emily Locke, Jordan Plieskatt, C Richter King, Camila H Coelho, Patrick E Duffy, Carole Long, 坪井 敬文, 三浦 憲豊, Yimin Wu, 石野 智子, Jonathan F Lovell
    • Organizer
      第81回日本寄生虫学会東日本支部大会
    • Related Report
      2022 Research-status Report
  • [Presentation] The 20th Awaji International Forum on Infection and Immunity.2022

    • Author(s)
      Tomoko Ishino.
    • Organizer
      Molecular mechanisms of malaria transmission to mammals via mosquito vectors.
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular mechanisms of malaria parasite transmission from mosquitoes to mammals.2022

    • Author(s)
      Tomoko Ishino.
    • Organizer
      第92回日本寄生虫学会大会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Molecular mechanisms of sporozoite transmission to mammals, the target of the first malaria vaccine2021

    • Author(s)
      Tomoko ISHINO
    • Organizer
      難病のプロテオ医学研究2021「The Genetics, Biology and Epidemiology of Diseases of Poverty」
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] マラリア原虫有性生殖体の細胞膜上に輸送されたPyMiGSは受精に関与する2020

    • Author(s)
      橘真由美、鳥居本美、馬場みなみ、坪井敬文、石野智子
    • Organizer
      第89回 日本寄生虫学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 熱帯熱マラリア原虫・生殖母体期におけるモーラークレフト分子の発現プロファイル解析2020

    • Author(s)
      面田彩馨、山崎望、橘真由美、石野智子、鳥居本美、坪井敬文、入子英幸
    • Organizer
      第89回 日本寄生虫学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Screening for candidate domains within Pfs230 that elicit transmission blocking antibody response2019

    • Author(s)
      Tachibana M, Miura K, Takashima E, Morita M, Nagaoka H, Zhou L, Long CA, Richter King C, Torii M, Tsuboi T, Ishino T
    • Organizer
      67th Annual meeting of American Society of Tropical Medicine & Hygene
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] 東京医科歯科大学 大学院医歯学総合研究科 寄生虫学・熱帯医学分野

    • URL

      https://sites.google.com/view/tmdu-parasitology

    • Related Report
      2023 Annual Research Report
  • [Remarks] 東京医科歯科大学 大学院医歯学総合研究科 環境社会医歯学講座 寄生虫学・熱帯医学分野

    • URL

      https://sites.google.com/view/tmdu-parasitology

    • Related Report
      2022 Research-status Report
  • [Remarks] 寄生虫学・熱帯医学分野

    • URL

      https://sites.google.com/view/tmdu-parasitology

    • Related Report
      2021 Research-status Report
  • [Remarks] プロテオサイエンスセンター 寄生病原体学部門

    • URL

      https://www.m.ehime-u.ac.jp/school/parasitology/

    • Related Report
      2019 Research-status Report

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Published: 2019-10-10   Modified: 2025-01-30  

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