The Jenner Institute and.
Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
JCI Insight. 2021 Dec 8;6(23):e152465. doi: 10.1172/jci.insight.152465.
Controlled human malaria infection (CHMI) provides a highly informative means to investigate host-pathogen interactions and enable in vivo proof-of-concept efficacy testing of new drugs and vaccines. However, unlike Plasmodium falciparum, well-characterized P. vivax parasites that are safe and suitable for use in modern CHMI models are limited. Here, 2 healthy malaria-naive United Kingdom adults with universal donor blood group were safely infected with a clone of P. vivax from Thailand by mosquito-bite CHMI. Parasitemia developed in both volunteers, and prior to treatment, each volunteer donated blood to produce a cryopreserved stabilate of infected RBCs. Following stringent safety screening, the parasite stabilate from one of these donors (PvW1) was thawed and used to inoculate 6 healthy malaria-naive United Kingdom adults by blood-stage CHMI, at 3 different dilutions. Parasitemia developed in all volunteers, who were then successfully drug treated. PvW1 parasite DNA was isolated and sequenced to produce a high-quality genome assembly by using a hybrid assembly method. We analyzed leading vaccine candidate antigens and multigene families, including the vivax interspersed repeat (VIR) genes, of which we identified 1145 in the PvW1 genome. Our genomic analysis will guide future assessment of candidate vaccines and drugs, as well as experimental medicine studies.
受控人体疟疾感染 (CHMI) 为研究宿主-病原体相互作用提供了一种非常有价值的手段，并能够对新药物和疫苗进行体内概念验证疗效测试。然而，与恶性疟原虫不同，安全且适合用于现代 CHMI 模型的特征明确的间日疟原虫寄生虫有限。在这里，2 名来自英国的无疟疾史的健康志愿者通过蚊子传播的 CHMI 安全感染了来自泰国的间日疟原虫克隆。两名志愿者均出现了寄生虫血症，并且在治疗前，每位志愿者都捐献了血液以产生冷冻保存的感染红细胞稳定剂。经过严格的安全筛选，从其中一名志愿者（PvW1）中解冻寄生虫稳定剂，并通过血期 CHMI 将其用于接种 6 名来自英国的无疟疾史的健康志愿者，接种剂量为 3 种不同的稀释度。所有志愿者均出现寄生虫血症，随后成功接受药物治疗。从 PvW1 寄生虫 DNA 中分离并测序，通过混合组装方法生成高质量的基因组组装。我们分析了主要的疫苗候选抗原和多基因家族，包括间日疟原虫间隔重复 (VIR) 基因，在 PvW1 基因组中鉴定出 1145 个。我们的基因组分析将指导未来对候选疫苗和药物的评估，以及实验医学研究。
