Neutralizing antibodies induced by recombinant virus-like particles of enterovirus 71 genotype C4 inhibit infection at pre- and post-attachment steps.
Neutralizing antibodies induced by recombinant virus-like particles of enterovirus 71 genotype C4 inhibit infection at pre- and post-attachment steps.
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DOI：
10.1371/journal.pone.0057601
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Huang Z
中科院分区：
文献类型：
--
作者：
Ku Z;Ye X;Huang X;Cai Y;Liu Q;Li Y;Su Z;Huang Z
肠道病毒71型（EV71）是手足口病的主要病原体，在亚太地区流行，导致幼儿的发病率和死亡率很高。实验性EV71疫苗诱导的抗体在体外能中和感染并被动保护动物模型免受致死性攻击，表明中和抗体在保护中起重要作用。然而，中和抗体如何在体外抑制感染仍不清楚。在本研究中，我们探讨了中和抗体对EV71病毒样颗粒（VLP）的机制。使用杆状病毒载体在昆虫细胞中产生EV 71基因型C4的重组VLP。用VLP免疫在小鼠中引起高滴度的EV71特异性抗体应答。抗VLP小鼠血清在体外有效中和EV71感染。发现抗VLP小鼠血清中的中和抗体主要靶向位于VP 1蛋白GH环的极其保守的表位（FGEHKQEKDLEYGAC）。中和性抗VLP抗血清能够有效地抑制病毒与靶细胞的结合。此外，用抗VLP抗血清对病毒结合的细胞进行附着后处理也中和了病毒感染，尽管所需的抗体浓度高于附着前处理。总的来说，我们的研究结果代表了一个有价值的理解EV71中和机制，并有很强的EV71疫苗开发的影响。
Enterovirus 71 (EV71) is a major causative agent of hand, foot and mouth disease, which has been prevalent in Asia–Pacific regions, causing significant morbidity and mortality in young children. Antibodies elicited by experimental EV71 vaccines could neutralize infection in vitro and passively protect animal models from lethal challenge, indicating that neutralizing antibodies play an essential role in protection. However, how neutralizing antibodies inhibit infection in vitro remains unclear. In the present study, we explored the mechanisms of neutralization by antibodies against EV71 virus-like particles (VLPs). Recombinant VLPs of EV71 genotype C4 were produced in insect cells using baculovirus vectors. Immunization with the VLPs elicited a high-titer, EV71-specific antibody response in mice. Anti-VLP mouse sera potently neutralized EV71 infection in vitro. The neutralizing antibodies in the anti-VLP mouse sera were found to target mainly an extremely conserved epitope (FGEHKQEKDLEYGAC) located at the GH loop of the VP1 protein. The neutralizing anti-VLP antisera were able to inhibit virus binding to target cells efficiently. In addition, post-attachment treatment of virus-bound cells with the anti-VLP antisera also neutralized virus infection, although the antibody concentration required was higher than that of the pre-attachment treatment. Collectively, our findings represent a valuable addition to the understanding of mechanisms of EV71 neutralization and have strong implications for EV71 vaccine development.
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