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Functional analysis of malaria vaccine candidate antigen GAMA

Research Project

Project/Area Number 21K06990
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49040:Parasitology-related
Research InstitutionTokyo Medical and Dental University (2022-2023)
Ehime University (2021)

Principal Investigator

NAGAOKA HIKARU  東京医科歯科大学, 大学院医歯学総合研究科, プロジェクト講師 (10757222)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsMalaria / Blood stage / GAMA / 赤血球期ステージ / 増殖阻害活性 / 新規ワクチン候補抗原 / モノクローナル抗体 / マラリア / コムギ無細胞 / ワクチン / 小麦無細胞
Outline of Research at the Start

マラリアワクチン開発は喫緊の課題である。そこで我々はコムギ無細胞系を基盤に、新規赤血球期ワクチン候補分子の同定や、ヒトタンパク質ライブラリーによる赤血球レセプター探索を精力的に行ってきた。本研究では、我々が近年見出した赤血球期ワクチン候補抗原であ るGPI-anchored merozoite antigen (GAMA)の赤血球侵入における機能を明らかにするために、モノクローナル抗体によるタンパク質相互作用ならびに原虫増殖に対する阻害活性の測定を行う。これにより原虫増殖阻害活性に重要なエピトープ情報を得ることで、GAMAを中心とした赤血球侵入機構の解明に大きく貢献する。

Outline of Final Research Achievements

The development of a malaria vaccine is very importance. In this study, we investigated the molecular function of GPI-anchored merozoite antigen (GAMA), this protein was recently discovered as a candidate antigen for blood stage vaccine. We want to clarify molecular function of this protein in erythrocyte invasion.
1) searched for GAMA interacting molecules using a human erythrocyte surface protein library, 2) generated the anti-GAMA monoclonal antibodies (mAb), and 3) measured growth inhibitory activity of the mAbs against Plasmodium falciparum.

Academic Significance and Societal Importance of the Research Achievements

熱帯熱マラリアゲノムが解読されて以来、欧米の研究者によりゲノムワイドな原虫組換えタンパク質の合成が試みられた。しかし、熱帯熱マラリア原虫遺伝子は76%ものAT含量でかつ繰り返し配列に富むため、大腸菌等の既存の発現系ではマラリア原虫の組換えタンパク質をほとんど合成できず、ポストゲノム時代のマラリアワクチン研究は大きな技術的障壁に直面していた。
本研究は、他の研究機関には無い独自のバイオリソースを駆使することによってのみ実行可能であり、世界に先駆けてマラリア原虫の分子機能を明らかにする手法を確立したことは重要である。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (15 results)

All 2024 2023 2022 2021

All Journal Article (9 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] GATS tag system is compatible with biotin labelling methods for protein analysis2023

    • Author(s)
      Yamada Kohdai、Soga Fumiya、Tokunaga Soh、Nagaoka Hikaru、Ozawa Tatsuhiko、Kishi Hiroyuki、Takashima Eizo、Sawasaki Tatsuya
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 10243-10243

    • DOI

      10.1038/s41598-023-36858-y

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of novel Plasmodium vivax proteins associated with protection against clinical malaria2023

    • Author(s)
      Mazhari Ramin、Takashima Eizo、Longley Rhea J.、Ruybal-Pesantez Shazia、White Michael T.、Kanoi Bernard N.、Nagaoka Hikaru、Kiniboro Benson、Siba Peter、Tsuboi Takafumi、Mueller Ivo
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 13

    • DOI

      10.3389/fcimb.2023.1076150

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Lipid-Binding Defective Dynamin 2 Mutant in Charcot-Marie-Tooth Disease Impairs Proper Actin Bundling and Actin Organization in Glomerular Podocytes2022

    • Author(s)
      Hamasaki Eriko、Wakita Natsuki、Yasuoka Hiroki、Nagaoka Hikaru、Morita Masayuki、Takashima Eizo、Uchihashi Takayuki、Takeda Tetsuya、Abe Tadashi、Lee Ji-Won、Iimura Tadahiro、Saleem Moin A、Ogo Naohisa、Asai Akira、Narita Akihiro、Takei Kohji、Yamada Hiroshi
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 10 Pages: 884509-884509

    • DOI

      10.3389/fcell.2022.884509

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Meta-Analysis of Human Antibodies Against Plasmodium falciparum Variable Surface and Merozoite Stage Antigens2022

    • Author(s)
      Takashima Eizo、Kanoi Bernard N.、Nagaoka Hikaru、Morita Masayuki、Hassan Ifra、Palacpac Nirianne M. Q.、Egwang Thomas G.、Horii Toshihiro、Gitaka Jesse、Tsuboi Takafumi
    • Journal Title

      Frontiers in Immunology

      Volume: 13 Pages: 887219-887219

    • DOI

      10.3389/fimmu.2022.887219

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Asexual Blood-Stage Malaria Vaccine Candidate PfRipr5: Enhanced Production in Insect Cells2022

    • Author(s)
      Correia Ricardo、Fernandes B、Castro Rute、Nagaoka Hikaru、Takashima Eizo、Tsuboi Takafumi、Fukushima Akihisa、Viebig Nicola K.、Depraetere Hilde、Alves Paula M.、Rold?o Ant?nio
    • Journal Title

      Frontiers in Bioengineering and Biotechnology

      Volume: 10 Pages: 908509-908509

    • DOI

      10.3389/fbioe.2022.908509

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recruitment of Irgb6 to the membrane is a direct trigger for membrane deformation2022

    • Author(s)
      Yamada Hiroshi、Abe Tadashi、Nagaoka Hikaru、Takashima Eizo、Nitta Ryo、Yamamoto Masahiro、Takei Kohji
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 12 Pages: 2022-2022

    • DOI

      10.3389/fcimb.2022.992198

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Novel Malaria Transmission-Blocking Vaccine Candidates2021

    • Author(s)
      Takashima Eizo、Tachibana Mayumi、Morita Masayuki、Nagaoka Hikaru、Kanoi Bernard N.、Tsuboi Takafumi
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 11 Pages: 1-8

    • DOI

      10.3389/fcimb.2021.805482

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterization of Naturally Acquired Immunity to a Panel of Antigens Expressed in Mature P. falciparum Gametocytes2021

    • Author(s)
      Muthui Michelle K.、Takashima Eizo、Omondi Brian R.、Kinya Christine、Muasya William I.、Nagaoka Hikaru、Mwai Kennedy W.、Orindi Benedict、Wambua Juliana、Bousema Teun、Drakeley Chris、Blagborough Andrew M.、Marsh Kevin、Bejon Philip、Kapulu Melissa C.
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 11 Pages: 774537-774537

    • DOI

      10.3389/fcimb.2021.774537

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Plasmodium yoelii Erythrocyte Binding Like Protein Interacts With Basigin, an Erythrocyte Surface Protein2021

    • Author(s)
      Yuguchi Takaaki、Kanoi Bernard N.、Nagaoka Hikaru、Miura Toyokazu、Ito Daisuke、Takeda Hiroyuki、Tsuboi Takafumi、Takashima Eizo、Otsuki Hitoshi
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 11 Pages: 656620-656620

    • DOI

      10.3389/fcimb.2021.656620

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 熱帯熱マラリア原虫ガメトサイト感染者を検出する抗体バイオマーカーの探索2024

    • Author(s)
      長岡ひかる1, 二瀬周哉2, Dorcas Gyamah Bredu3, Linda Eva Amoah3, 高島英造2.
    • Organizer
      第93回 日本寄生虫学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Plasmodium falciparum PF3D7_0715200 is a merozoite surface protein that induces antibodies with mild growth inhibitory activity.2022

    • Author(s)
      長岡ひかる
    • Organizer
      ASTMH 2022 Annual Meeting.
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 熱帯熱マラリア原虫メロゾイト侵入機構解明に向けた原虫増殖活性を有する抗 Ripr モノクローナル抗体の作出2022

    • Author(s)
      長岡 ひかる,福島 晃久,坪井 敬文,高島 英造
    • Organizer
      第91回日本寄生虫学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 赤血球期熱帯熱マラリア原虫PHISTcタンパク質Pf3D7_0801000の性状解析2021

    • Author(s)
      長岡ひかる, カノイ・バーナード, 森田将之, 中田貴敬, ニリアン・パラクパック, 堀井俊宏, 坪井敬文, 高島英造
    • Organizer
      第90回日本寄生虫学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 三日熱マラリア原虫タンパク質MSP7の生化学的解析2021

    • Author(s)
      長岡ひかる, 小川晃輝, カノイ・バーナード, 坪井敬文, 高島英造
    • Organizer
      第94回日本生化学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Reverse vaccinology approach for discovery of novel malaria blood-stage vaccine candidates: The case of Ripr5.2021

    • Author(s)
      Hikaru Nagaoka
    • Organizer
      9th Academic symposium, The Genetics, Biology, and Epidemiology of Diseases of Poverty.
    • Related Report
      2021 Research-status Report
    • Invited

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Published: 2021-04-28   Modified: 2025-01-30  

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