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A comprehensive model for assessment of liver stage therapies targeting Plasmodium vivax and Plasmodium falciparum

Author

Listed:
  • Alison Roth

    (University of South Florida)

  • Steven P. Maher

    (University of South Florida
    University of Georgia)

  • Amy J. Conway

    (University of South Florida)

  • Ratawan Ubalee

    (Armed Forces Research Institute of Medical Sciences (AFRIMS))

  • Victor Chaumeau

    (University of Oxford
    Faculty of Tropical Medicine, Mahidol University)

  • Chiara Andolina

    (University of Oxford
    Faculty of Tropical Medicine, Mahidol University)

  • Stephen A. Kaba

    (Walter Reed Army Institute of Research)

  • Amélie Vantaux

    (Institut Pasteur du Cambodge)

  • Malina A. Bakowski

    (California Institute for Biomedical Research (Calibr))

  • Richard Thomson-Luque

    (University of South Florida)

  • Swamy Rakesh Adapa

    (University of South Florida)

  • Naresh Singh

    (University of South Florida)

  • Samantha J. Barnes

    (University of South Florida)

  • Caitlin A. Cooper

    (University of Georgia)

  • Mélanie Rouillier

    (Medicines for Malaria Venture)

  • Case W. McNamara

    (California Institute for Biomedical Research (Calibr))

  • Sebastian A. Mikolajczak

    (Center for Infectious Disease Research)

  • Noah Sather

    (Center for Infectious Disease Research)

  • Benoît Witkowski

    (California Institute for Biomedical Research (Calibr))

  • Brice Campo

    (Medicines for Malaria Venture)

  • Stefan H. I. Kappe

    (Center for Infectious Disease Research)

  • David E. Lanar

    (Walter Reed Army Institute of Research)

  • François Nosten

    (University of Oxford
    Faculty of Tropical Medicine, Mahidol University)

  • Silas Davidson

    (Armed Forces Research Institute of Medical Sciences (AFRIMS))

  • Rays H. Y. Jiang

    (University of South Florida)

  • Dennis E. Kyle

    (University of South Florida
    University of Georgia)

  • John H. Adams

    (University of South Florida)

Abstract

Malaria liver stages represent an ideal therapeutic target with a bottleneck in parasite load and reduced clinical symptoms; however, current in vitro pre-erythrocytic (PE) models for Plasmodium vivax and P. falciparum lack the efficiency necessary for rapid identification and effective evaluation of new vaccines and drugs, especially targeting late liver-stage development and hypnozoites. Herein we report the development of a 384-well plate culture system using commercially available materials, including cryopreserved primary human hepatocytes. Hepatocyte physiology is maintained for at least 30 days and supports development of P. vivax hypnozoites and complete maturation of P. vivax and P. falciparum schizonts. Our multimodal analysis in antimalarial therapeutic research identifies important PE inhibition mechanisms: immune antibodies against sporozoite surface proteins functionally inhibit liver stage development and ion homeostasis is essential for schizont and hypnozoite viability. This model can be implemented in laboratories in disease-endemic areas to accelerate vaccine and drug discovery research.

Suggested Citation

  • Alison Roth & Steven P. Maher & Amy J. Conway & Ratawan Ubalee & Victor Chaumeau & Chiara Andolina & Stephen A. Kaba & Amélie Vantaux & Malina A. Bakowski & Richard Thomson-Luque & Swamy Rakesh Adapa , 2018. "A comprehensive model for assessment of liver stage therapies targeting Plasmodium vivax and Plasmodium falciparum," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04221-9
    DOI: 10.1038/s41467-018-04221-9
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    Cited by:

    1. Hao-Chi Hsu & Daqiang Li & Wenhu Zhan & Jianxiang Ye & Yi Jing Liu & Annie Leung & Junling Qin & Benigno Crespo & Francisco-Javier Gamo & Hao Zhang & Liwang Cui & Alison Roth & Laura A. Kirkman & Huil, 2023. "Structures revealing mechanisms of resistance and collateral sensitivity of Plasmodium falciparum to proteasome inhibitors," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Diego Rodríguez-Hernández & Kamalakannan Vijayan & Rachael Zigweid & Michael K. Fenwick & Banumathi Sankaran & Wanlapa Roobsoong & Jetsumon Sattabongkot & Elizabeth K. K. Glennon & Peter J. Myler & Pe, 2023. "Identification of potent and selective N-myristoyltransferase inhibitors of Plasmodium vivax liver stage hypnozoites and schizonts," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Annie S. P. Yang & Devanjali Dutta & Kai Kretzschmar & Delilah Hendriks & Jens Puschhof & Huili Hu & Kim E. Boonekamp & Youri Waardenburg & Susana M. Chuva de Sousa Lopes & Geert-Jan Gemert & Johannes, 2023. "Development of Plasmodium falciparum liver-stages in hepatocytes derived from human fetal liver organoid cultures," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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