Controlled human malaria infection with a clone of Plasmodium vivax with high-quality genome assembly.

Controlled human malaria infection with a clone of Plasmodium vivax with high-quality genome assembly.
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DOI:
10.1172/jci.insight.152465
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发表时间:
2021-12-08
期刊:
影响因子:
8
通讯作者:
Draper SJ
Draper SJ
中科院分区:
医学1区
文献类型:
--
作者:
Minassian AM;Themistocleous Y;Silk SE;Barrett JR;Kemp A;Quinkert D;Nielsen CM;Edwards NJ;Rawlinson TA;Ramos Lopez F;Roobsoong W;Ellis KJ;Cho JS;Aunin E;Otto TD;Reid AJ;Bach FA;Labbé GM;Poulton ID;Marini A;Zaric M;Mulatier M;Lopez Ramon R;Baker M;Mitton CH;Sousa JC;Rachaphaew N;Kumpitak C;Maneechai N;Suansomjit C;Piteekan T;Hou MM;Khozoee B;McHugh K;Roberts DJ;Lawrie AM;Blagborough AM;Nugent FL;Taylor IJ;Johnson KJ;Spence PJ;Sattabongkot J;Biswas S;Rayner JC;Draper SJ

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受控制的人疟疾感染(CHMI)为调查宿主-病原体相互作用和对新药和疫苗进行体内概念有效性验证提供了一种信息丰富的手段。然而,与恶性疟原虫不同的是,在现代CHMI模型中安全且适合使用的特征明确的间日疟原虫是有限的。在这里,2名健康的无疟疾的英国成年人,他们具有通用的供血血型,通过蚊子叮咬的CHMI安全地感染了来自泰国的间日疟原虫克隆。两名志愿者都出现了寄生虫病,在治疗之前,每名志愿者都捐献了血液,以产生冷冻保存的感染红细胞稳定物。经过严格的安全筛选后,将其中一名供体(PvW1)的稳定寄生虫解冻,用3种不同稀释度的血期CHMI接种6名健康的未患疟疾的英国成年人。所有志愿者都出现了寄生虫病,然后成功地对他们进行了药物治疗。对PvW1寄生虫DNA进行分离和测序,采用杂交组装法获得高质量的基因组组装。我们分析了主要的候选疫苗抗原和多基因家族,包括间日疟原虫穿插重复序列(VIR)基因,其中我们在PvW1基因组中鉴定了1145个。我们的基因组分析将指导未来候选疫苗和药物的评估,以及实验医学研究。
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.
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