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Development of an Ectopic huLiver Model for Plasmodium Liver Stage Infection

Gabriela Samayoa Reyes, Siobhan Flaherty, Kristina S. Wickham, Sara Viera-Morilla, Pamela Strauch, Alison Roth, Laura Padrón, View ORCID ProfileConner Jackson, Patricia Meireles, David Calvo, Wanlapa Roobsoong, Niwat Kangwanrangsan, Jetsumon Sattabongkot, Gregory Reichard, Maria José Lafuente-Monasterio, View ORCID ProfileRosemary Rochford
doi: https://doi.org/10.1101/2022.12.01.518796
Gabriela Samayoa Reyes
1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
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Siobhan Flaherty
1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
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Kristina S. Wickham
2Department of Drug Discovery, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
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Sara Viera-Morilla
3Diseases of the Developing World, Infectious Diseases-Centre for Excellence in Drug Discovery (ID CEDD), GlaxoSmithKline, Tres Cantos, Madrid, Spain
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Pamela Strauch
1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
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Alison Roth
2Department of Drug Discovery, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
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Laura Padrón
3Diseases of the Developing World, Infectious Diseases-Centre for Excellence in Drug Discovery (ID CEDD), GlaxoSmithKline, Tres Cantos, Madrid, Spain
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Conner Jackson
1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
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  • ORCID record for Conner Jackson
Patricia Meireles
3Diseases of the Developing World, Infectious Diseases-Centre for Excellence in Drug Discovery (ID CEDD), GlaxoSmithKline, Tres Cantos, Madrid, Spain
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David Calvo
3Diseases of the Developing World, Infectious Diseases-Centre for Excellence in Drug Discovery (ID CEDD), GlaxoSmithKline, Tres Cantos, Madrid, Spain
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Wanlapa Roobsoong
4Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
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Niwat Kangwanrangsan
5Pathobiology Department, Faculty of Science, Mahidol University, Bangkok, Thailand
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Jetsumon Sattabongkot
4Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
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Gregory Reichard
2Department of Drug Discovery, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
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Maria José Lafuente-Monasterio
3Diseases of the Developing World, Infectious Diseases-Centre for Excellence in Drug Discovery (ID CEDD), GlaxoSmithKline, Tres Cantos, Madrid, Spain
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Rosemary Rochford
1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
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  • ORCID record for Rosemary Rochford
  • For correspondence: rosemary.rochford@cuanschutz.edu
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Abstract

Early Plasmodium falciparum and P. vivax infection requires parasite replication within host hepatocytes, referred to as liver stage (LS). However, limited understanding of infection dynamics in human LS exists due to species-specificity challenges. Reported here is a reproducible, easy-to-manipulate, and moderate-cost in vivo model to study human Plasmodium LS in mice; the ectopic huLiver model. Ectopic huLiver tumors were generated through subcutaneous injection of the HC-04 cell line and shown to be infectible by both freshly dissected sporozoites and through the bite of infected mosquitoes. Evidence for complete LS development was supported by the transition to blood-stage infection in mice engrafted with human erythrocytes. Additionally, this model was successfully evaluated for its utility in testing antimalarial therapeutics, as supported by primaquine acting as a causal prophylactic against P. falciparum. Presented here is a new platform for the study of human Plasmodium infection with the potential to aid in drug discovery.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
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Posted December 02, 2022.
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Development of an Ectopic huLiver Model for Plasmodium Liver Stage Infection
Gabriela Samayoa Reyes, Siobhan Flaherty, Kristina S. Wickham, Sara Viera-Morilla, Pamela Strauch, Alison Roth, Laura Padrón, Conner Jackson, Patricia Meireles, David Calvo, Wanlapa Roobsoong, Niwat Kangwanrangsan, Jetsumon Sattabongkot, Gregory Reichard, Maria José Lafuente-Monasterio, Rosemary Rochford
bioRxiv 2022.12.01.518796; doi: https://doi.org/10.1101/2022.12.01.518796
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Development of an Ectopic huLiver Model for Plasmodium Liver Stage Infection
Gabriela Samayoa Reyes, Siobhan Flaherty, Kristina S. Wickham, Sara Viera-Morilla, Pamela Strauch, Alison Roth, Laura Padrón, Conner Jackson, Patricia Meireles, David Calvo, Wanlapa Roobsoong, Niwat Kangwanrangsan, Jetsumon Sattabongkot, Gregory Reichard, Maria José Lafuente-Monasterio, Rosemary Rochford
bioRxiv 2022.12.01.518796; doi: https://doi.org/10.1101/2022.12.01.518796

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