In vitro and in vivo characterization of a new enterovirus type 71-specific human intravenous immunoglobulin manufactured from selected plasma donors
In vitro and in vivo characterization of a new enterovirus type 71-specific human intravenous immunoglobulin manufactured from selected plasma donors
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DOI：
10.1016/j.jcv.2011.05.002
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发表时间：
2011-08-01
影响因子：
8.8
通讯作者：
Qin, Cheng-Feng
中科院分区：
文献类型：
--
作者：
Cao, Rui-Yuan;Han, Jian-Feng;Qin, Cheng-Feng
背景：71型肠病毒（EV71）在幼儿中引起大规模暴发，造成大量死亡率，目前尚无特异性抗病毒治疗方法。基于抗体的治疗是致命EV71感染的一种有希望的替代策略。我们之前的数据显示，抗ev71中和抗体存在于中国很大比例的献血者中。目的：制备一种含有高滴度抗EV71中和抗体的新型人静脉注射免疫球蛋白（IVIG）产品，并观察其对小鼠EV71致死性感染的治疗效果。研究设计：从选定的中国献血者收集含有高滴度中和抗体的血浆，按照标准程序加工成药物级IVIG制剂。体外中和实验和体内乳鼠保护实验对这些ev71特异性IVIG产品的作用进行了表征。在哺乳小鼠模型上进一步观察了其对致死性EV71攻毒的治疗效果。结果：选取约12%的正常血浆单位制备EV71-IVIG制剂，体外和体内药效数据显示，这些EV71特异性IVIG制剂富含针对EV71的中和抗体。此外，在哺乳小鼠模型中，EV71特异性IVIG治疗被证明可以以剂量和时间依赖的方式保护小鼠免受致命的EV71攻击。结论：这项临床前研究表明，这些“量身定制”的EV71- ivig制剂来自EV71流行地区的选定血浆供者，可能是致命EV71感染的一种有希望的治疗选择，未来需要进一步的临床试验。(c) 2011 Elsevier b.v.保留所有权利。
Background: Enterovirus type 71 (EV71) causes large outbreaks with significant mortality among young children, and no specific antiviral treatment is currently available. Antibody-based therapy represents a promising alternative strategy for lethal EV71 infection. Our previous data has shown that anti-EV71 neutralization antibodies were present in a significant proportion of blood donors in China.Objectives: To produce a new human intravenous immunoglobulin (IVIG) product containing high titer anti-EV71 neutralizing antibodies and investigate its therapeutic efficacy against lethal EV71 infection in a murine model.Study design: Plasma units that contained high titer neutralizing antibodies from selected Chinese donors were pooled and processed into pharmaceutical grade IVIG preparations according to the standard procedure. The efficacy of these EV71-specific IVIG product was characterized in vitro by neutralization assay and in vivo by suckling mouse protection testing. The therapeutic effects against lethal EV71 challenge were further assayed in a suckling mouse model.Results: About 12% of the normal plasma units were selected and pooled to manufacture the EV71-IVIG preparations, and in vitro and in vivo efficacy data showed that these EV71-specific IVIG preparations were enriched with neutralizing antibodies against EV71. Furthermore, treatment with EV71-specific IVIG was evidenced to confer protection against lethal EV71 challenge in a dose-and time-dependent manner in the suckling mouse model.Conclusions: This preclinical study indicates that these "tailor-made" EV71-IVIG preparations manufactured from selected plasma donors in EV71-endemic areas may represent a promising therapeutic option for the lethal EV71 infections, and further clinical trials should be warranted in the future. (c) 2011 Elsevier B. V. All rights reserved.