Publication: A comprehensive model for assessment of liver stage therapies targeting Plasmodium vivax and Plasmodium falciparum
Issued Date
2018-12-01
Resource Type
ISSN
20411723
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2-s2.0-85046866462
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Mahidol University
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SCOPUS
Bibliographic Citation
Nature Communications. Vol.9, No.1 (2018)
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, 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 A comprehensive model for assessment of liver stage therapies targeting Plasmodium vivax and Plasmodium falciparum. Nature Communications. Vol.9, No.1 (2018). doi:10.1038/s41467-018-04221-9 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/44988
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Title
A comprehensive model for assessment of liver stage therapies targeting Plasmodium vivax and Plasmodium falciparum
Author(s)
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
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 Contributor(s)
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
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
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.