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

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 and John H. Adams ()
Additional contact information
Alison Roth: University of South Florida
Steven P. Maher: University of South Florida
Amy J. Conway: University of South Florida
Ratawan Ubalee: Armed Forces Research Institute of Medical Sciences (AFRIMS)
Victor Chaumeau: University of Oxford
Chiara Andolina: University of Oxford
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
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
John H. Adams: University of South Florida

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04221-9

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DOI: 10.1038/s41467-018-04221-9

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