Structure, Immunogenicity and Protective Mechanism of an Engineered Enterovirus 71-Like Particle Vaccine Mimicking 80S Empty Capsid
Structure, Immunogenicity and Protective Mechanism of an Engineered Enterovirus 71-Like Particle Vaccine Mimicking 80S Empty Capsid
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模仿 80S 空衣壳的工程肠道病毒 71 样颗粒疫苗的结构、免疫原性和保护机制
DOI：
10.1128/jvi.01330-17
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发表时间：
2017
影响因子：
5.4
通讯作者：
Zhong Huang
中科院分区：
文献类型：
--
作者：
Xiaoli Wang;Zhiqiang Ku;Xiang Zhang;Xiaohua Ye;Jinhuan Chen;Qingwei Liu;Wei Zhang;Chao Zhang;Zhenglin Fu;Xia Jin;Yao Cong;Zhong Huang
肠道病毒71型（EV 71）是严重手足口病的主要病原体，每年影响亚太地区数百万儿童。在这项研究中，我们设计了一种新的EV 71病毒样颗粒（VLP），缺乏VP 4（因此命名为VLP.VP4），并研究了其结构，抗原性和疫苗的潜力。将VLP.VP4的冷冻电子显微镜（cryo-EM）结构重建为3.71-A分辨率。结构和生物化学分析的结果显示，VLP.VP4类似于病毒脱壳过程的终产物，即80 S空衣壳。VLP. VP 4能够引发高滴度中和抗体，并完全保护小鼠免受致命病毒攻击。在细胞水平上，抗VLP、VP 4血清通过抑制病毒的粘附和内化，在粘附前后发挥中和作用;在分子水平上，抗VLP、VP 4血清可阻断EV 71与其主要受体之间的多种相互作用。我们的研究提供了一个更好的理解EV 71衣壳组装，并提供了重要的信息，设计和开发新一代疫苗的EV 71，也许其他肠道病毒，以及。
Enterovirus 71 (EV71) is the major causative agent of severe hand, foot, and mouth disease, which affects millions of young children in the Asia-Pacific region annually. In this study, we engineered a novel EV71 virus-like particle (VLP) that lacks VP4 (therefore designated VLP.VP4) and investigated its structure, antigenicity, and vaccine potential. The cryo-electron microscopy (cryo-EM) structure of VLP.VP4 was reconstructed to 3.71-A resolution. Results from structural and biochemical analyses revealed that VLP.VP4 resembles the end product of the viral uncoating process, the 80S empty capsid. VLP.VP4 is able to elicit high-titer neutralizing antibodies and to fully protect mice against lethal viral challenge. Mechanistic studies showed that, at the cellular level, the anti-VLP.VP4 sera exert neutralization effects at both preand postattachment stages by inhibiting both virus attachment and internalization, and at the molecular level, the antisera can block multiple interactions between EV71 and its key receptors. Our study gives a better understanding of EV71 capsid assembly and provides important information for the design and development of new-generation vaccines for EV71, and perhaps for other enteroviruses, as well.