A Humanized Mouse Model for Plasmodium vivax to Test Interventions that Block Liver Stage to Blood Stage Transition and Blood Stage Infection

Carola Schäfer; Wanlapa Roobsoong; Niwat Kangwanrangsan; Martino Bardelli; Thomas A Rawlinson; Nicholas Dambrauskas; Olesya Trakhimets; Chaitra Parthiban; Debashree Goswami; Laura M Reynolds; Spencer Y Kennedy; Erika L Flannery; Sean C Murphy; D Noah Sather; Simon J Draper; Jetsumon Sattabongkot; Sebastian A Mikolajczak; Stefan H I Kappe

doi:10.1016/j.isci.2020.101381

A Humanized Mouse Model for Plasmodium vivax to Test Interventions that Block Liver Stage to Blood Stage Transition and Blood Stage Infection

iScience. 2020 Aug 21;23(8):101381. doi: 10.1016/j.isci.2020.101381. Epub 2020 Jul 18.

Authors

Carola Schäfer¹, Wanlapa Roobsoong², Niwat Kangwanrangsan³, Martino Bardelli⁴, Thomas A Rawlinson⁴, Nicholas Dambrauskas¹, Olesya Trakhimets¹, Chaitra Parthiban⁵, Debashree Goswami¹, Laura M Reynolds¹, Spencer Y Kennedy¹, Erika L Flannery¹, Sean C Murphy⁵, D Noah Sather⁶, Simon J Draper⁴, Jetsumon Sattabongkot², Sebastian A Mikolajczak¹, Stefan H I Kappe⁷

Affiliations

¹ Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA.
² Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
³ Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
⁴ The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
⁵ Departments of Laboratory Medicine and Microbiology and Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA 98109, USA.
⁶ Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA; Department of Pediatrics, University of Washington, Seattle, WA 98105, USA; Department of Global Health, University of Washington, Seattle, WA 98105, USA.
⁷ Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA; Department of Pediatrics, University of Washington, Seattle, WA 98105, USA; Department of Global Health, University of Washington, Seattle, WA 98105, USA. Electronic address: stefan.kappe@seattlechildrens.org.

Abstract

The human malaria parasite Plasmodium vivax remains vastly understudied, mainly due to the lack of suitable laboratory models. Here, we report a humanized mouse model to test interventions that block P. vivax parasite transition from liver stage infection to blood stage infection. Human liver-chimeric FRGN huHep mice infected with P. vivax sporozoites were infused with human reticulocytes, allowing transition of exo-erythrocytic merozoites to reticulocyte infection and development into all erythrocytic forms, including gametocytes, in vivo. In order to test the utility of this model for preclinical assessment of interventions, the invasion blocking potential of a monoclonal antibody targeting the essential interaction of the P. vivax Duffy Binding Protein with the Duffy antigen receptor was tested by passive immunization. This antibody inhibited invasion by over 95%, providing unprecedented in vivo evidence that PvDBP constitutes a promising blood stage vaccine candidate and proving our model highly suitable to test blood stage interventions.

Keywords: Microbiology; Model Organism; Parasitology.

Abstract

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