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

• Main Authors: 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, Naresh Singh, Samantha J. Barnes, Caitlin A. Cooper, Mélanie Rouillier, Case W. McNamara, Sebastian A. Mikolajczak, Noah Sather, Benoît Witkowski, Brice Campo, Stefan H.I. Kappe, David E. Lanar, François Nosten, Silas Davidson, Rays H.Y. Jiang, Dennis E. Kyle, John H. Adams
• Other Authors: Institut Pasteur du Cambodge
• Format: Article
• Published: 2019
• Subjects: Biochemistry, Genetics and Molecular Biology; Chemistry; Physics and Astronomy
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/44988
• Institution: Mahidol University

© 2018 The Author(s). 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.