A new class of broadly neutralizing antibodies that target the glycan loop of Zika virus envelope protein
A new class of broadly neutralizing antibodies that target the glycan loop of Zika virus envelope protein
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一类新型广泛中和抗体，针对寨卡病毒包膜蛋白的聚糖环
DOI：
10.1038/s41421-019-0140-8
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发表时间：
2020-02-04
期刊：
影响因子：
33.5
通讯作者：
Huang, Zhong
中科院分区：
文献类型：
--
作者：
Qu, Panke;Zhang, Chao;Huang, Zhong
寨卡病毒（ZIKV）感染对人类健康构成严重威胁。然而，目前没有获得许可的疫苗或治疗药物可用于ZIKV。我们先前已经表明，重组ZIKV E80蛋白诱导有效的中和抗体应答并保护小鼠免受致命病毒攻击。在本研究中，我们从E80免疫的小鼠中分离了五种ZIKV中和单克隆抗体（mAb）。这五种mAb特异性结合并中和亚洲谱系ZIKV毒株。表位作图显示，所有的5个单克隆抗体识别一个新的线性表位位于E蛋白结构域I的聚糖环。序列比对显示，该表位在ZIKV中极其保守，但在ZIKV和其他黄病毒之间高度可变。因此，这五种mAb形成一类新的抗ZIKV抗体，其对亚洲谱系ZIKV表现出广谱中和。发现该mAb类别的代表5F8主要在附着后病毒进入过程的早期阶段在体外发挥抑制功能。重要的是，mAb 5F8能够在ZIKV致死感染的小鼠模型中赋予完全保护。我们的结果对于开发抗ZIKV疫苗和治疗性mAb具有强烈的意义。
Zika virus (ZIKV) infection poses a serious threat to human health. However, no licensed vaccine or therapeutic drug is currently available for ZIKV. We have previously shown that recombinant ZIKV E80 protein induced potent neutralizing antibody response and protected mice from lethal viral challenge. In the present study, we isolated five ZIKV neutralizing monoclonal antibodies (mAbs) from E80-immunized mice. These five mAbs specifically bound and neutralized Asian-lineage ZIKV strains. Epitope mapping revealed that all of the five mAbs recognized a novel linear epitope located on the glycan loop of E protein domain I. Sequence alignment revealed that the epitope was extremely conserved in ZIKV but highly variable between ZIKV and other flaviviruses. Thus, these five mAbs form a new class of anti-ZIKV antibodies exhibiting broad-spectrum neutralization on Asian-lineage ZIKV. A representative of this mAb class, 5F8, was found to exert inhibitory function in vitro primarily at the early stage of the post-attachment viral entry process. Importantly, mAb 5F8 was able to confer full protection in a mouse model of ZIKV lethal infection. Our results have strong implications for developing anti-ZIKV vaccines and therapeutic mAbs.