Basigin is a druggable target for host-oriented antimalarial interventions.
Basigin is a druggable target for host-oriented antimalarial interventions.
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DOI：
10.1084/jem.20150032
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发表时间：
2015-07-27
期刊：
影响因子：
--
通讯作者：
Wright GJ
中科院分区：
文献类型：
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作者：
Zenonos ZA;Dummler SK;Müller-Sienerth N;Chen J;Preiser PR;Rayner JC;Wright GJ
Zenonos等人报道了恶性疟原虫疟疾的新疗法的开发。针对红细胞侵袭必需的basigin-a受体的重组嵌合抗体抑制寄生虫的侵袭，并在体内快速清除已建立的血液阶段感染。恶性疟原虫是造成最致命的疟疾的寄生虫，疟疾是一种传染病，造成很大比例的儿童死亡，并对许多国家的社会经济发展构成重大障碍。虽然存在抗疟药物，但抗药性寄生虫的反复出现和传播限制了它们的有效寿命。另一种可能限制耐药寄生虫进化的策略是针对寄生虫生长所必需和普遍需要的宿主因素。宿主靶向疗法已成功应用于其他传染病，但从未尝试用于疟疾。在这里，我们报告了一种重组嵌合抗体（Ab-1）的发展对basigin，红细胞受体寄生虫入侵作为一个假定的抗疟疾治疗所必需的。Ab-1抑制PfRH 5-basigin相互作用，并有效地阻断所有测试的寄生虫菌株的红细胞侵入。重要的是，Ab-1在体内感染模型中快速清除了已建立的恶性疟原虫血液阶段感染，而没有明显的毒性。总的来说，我们的数据表明，靶向宿主basigin的抗体或其他治疗剂可能是感染多重耐药恶性疟原虫的患者的有效治疗方法。
Zenonos et al. report the development of a new therapeutic for P. falciparum malaria. A recombinant chimeric antibody targeting basigin—a receptor essential for erythrocyte invasion—inhibited parasite invasion and rapidly cleared an established blood-stage infection in vivo. Plasmodium falciparum is the parasite responsible for the most lethal form of malaria, an infectious disease that causes a large proportion of childhood deaths and poses a significant barrier to socioeconomic development in many countries. Although antimalarial drugs exist, the repeated emergence and spread of drug-resistant parasites limit their useful lifespan. An alternative strategy that could limit the evolution of drug-resistant parasites is to target host factors that are essential and universally required for parasite growth. Host-targeted therapeutics have been successfully applied in other infectious diseases but have never been attempted for malaria. Here, we report the development of a recombinant chimeric antibody (Ab-1) against basigin, an erythrocyte receptor necessary for parasite invasion as a putative antimalarial therapeutic. Ab-1 inhibited the PfRH5-basigin interaction and potently blocked erythrocyte invasion by all parasite strains tested. Importantly, Ab-1 rapidly cleared an established P. falciparum blood-stage infection with no overt toxicity in an in vivo infection model. Collectively, our data demonstrate that antibodies or other therapeutics targeting host basigin could be an effective treatment for patients infected with multi-drug resistant P. falciparum.