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
Affiliations
Carola Schäfer
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA
Wanlapa Roobsoong
Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
Niwat Kangwanrangsan
Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
Martino Bardelli
The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Thomas A. Rawlinson
The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Nicholas Dambrauskas
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA
Olesya Trakhimets
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA
Chaitra Parthiban
Departments of Laboratory Medicine and Microbiology and Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA 98109, USA
Debashree Goswami
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA
Laura M. Reynolds
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA
Spencer Y. Kennedy
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA
Erika L. Flannery
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA
Sean C. Murphy
Departments of Laboratory Medicine and Microbiology and Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA 98109, USA
D. Noah Sather
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
Simon J. Draper
The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Jetsumon Sattabongkot
Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
Sebastian A. Mikolajczak
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA
Stefan H.I. Kappe
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; Corresponding author
Summary: 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.
