文章基本信息

标题：A Humanized Mouse Model for Plasmodium vivax to Test Interventions that Block Liver Stage to Blood Stage Transition and Blood Stage Infection
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作者：Carola Schäfer ; Wanlapa Roobsoong ; Niwat Kangwanrangsan 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：8
页码：1-21
DOI：10.1016/j.isci.2020.101381
语种：English
出版社：Elsevier
摘要：SummaryThe human malaria parasitePlasmodium vivaxremains vastly understudied, mainly due to the lack of suitable laboratory models. Here, we report a humanized mouse model to test interventions that blockP. vivaxparasite transition from liver stage infection to blood stage infection. Human liver-chimeric FRGN huHep mice infected withP. vivaxsporozoites 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 theP. vivaxDuffy Binding Protein with the Duffy antigen receptor was tested by passive immunization. This antibody inhibited invasion by over 95%, providing unprecedentedin vivoevidence that PvDBP constitutes a promising blood stage vaccine candidate and proving our model highly suitable to test blood stage interventions.Graphical AbstractDisplay OmittedHighlights•A humanized mouse model allowsP. vivaxliver stage to blood stage transition•This model is highly suitable to testP. vivaxblood stage interventionsin vivo•P. vivaxparasites can commit to sexual development as they emerge from the liverMicrobiology; Model Organism; Parasitology