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Title: A comprehensive model for assessment of liver stage therapies targeting Plasmodium vivax and Plasmodium falciparum
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
Institut Pasteur du Cambodge
University of South Florida Health
The University of Georgia
Armed Forces Research Institute of Medical Sciences, Thailand
Walter Reed Army Institute of Research
Mahidol University
Nuffield Department of Clinical Medicine
Center for Infectious Disease Research
Medicines for Malaria Venture
California Institute for Biomedical Research
Keywords: Biochemistry, Genetics and Molecular Biology;Chemistry;Physics and Astronomy
Issue Date: 1-Dec-2018
Citation: Nature Communications. Vol.9, No.1 (2018)
Abstract: © 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.
ISSN: 20411723
Appears in Collections:Scopus 2018

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