Human IgG subclasses against enterovirus Type 71: neutralization versus antibody dependent enhancement of infection.

Human IgG subclasses against enterovirus Type 71: neutralization versus antibody dependent enhancement of infection.
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抗 71 型肠道病毒的人 IgG 亚类:中和作用与抗体依赖性感染增强作用

DOI:
10.1371/journal.pone.0064024
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Qin CF
Qin CF
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cao RY;Dong DY;Liu RJ;Han JF;Wang GC;Zhao H;Li XF;Deng YQ;Zhu SY;Wang XY;Lin F;Zhang FJ;Chen W;Qin ED;Qin CF

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新出现的人类肠道病毒71型(EV71)对公共卫生构成日益严重的威胁,目前还没有疫苗或特异性抗病毒药物。人静脉注射免疫球蛋白(IVIG)临床上用于治疗严重的EV71感染。然而,EV71感染的抗体依赖性增强(ADE)的发现说明了抗体在控制EV71感染中的复杂作用。本研究采用蛋白A结合亲和层析柱,通过pH梯度洗脱,对不同批次的中国人IVIG制剂进行IgG亚类分离,以确定各IgG亚类在中和和增强EV71感染中的不同作用。然后分别测定纯化的各IgG亚类对EV71感染的中和和ADE能力。人IVIG的中和活性主要由IgG1亚类介导,其次由IgG2亚类介导。有趣的是,IgG3级分没有中和活性,但在体外增强了EV71感染。这些结果揭示了人IgG亚类在EV71感染中的不同作用,这对于EV71重症疾病的免疫治疗和疫苗的合理设计至关重要。
The emerging human enterovirus 71 (EV71) represents a growing threat to public health, and no vaccine or specific antiviral is currently available. Human intravenous immunoglobulin (IVIG) is clinical used in treating severe EV71 infections. However, the discovery of antibody dependent enhancement (ADE) of EV71 infection illustrates the complex roles of antibody in controlling EV71 infection. In this study, to identify the distinct role of each IgG subclass on neutralization and enhancement of EV71 infection, different lots of pharmaceutical IVIG preparations manufactured from Chinese donors were used for IgG subclass fractionation by pH gradient elution with the protein A-conjugated affinity column. The neutralization and ADE capacities on EV71 infection of each purified IgG subclass were then assayed, respectively. The neutralizing activity of human IVIG is mainly mediated by IgG1 subclass and to less extent by IgG2 subclass. Interestingly, IgG3 fraction did not have neutralizing activity but enhanced EV71 infection in vitro. These results revealed the different roles of human IgG subclasses on EV71 infection, which is of critical importance for the rational design of immunotherapy and vaccines against severe EV71 diseases.
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