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.

中文翻译：

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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。

寨卡病毒（ZIKV）感染对人类健康构成严重威胁。然而，目前尚无针对 ZIKV 的许可疫苗或治疗药物。我们之前已经证明，重组 ZIKV E80 蛋白可诱导有效的中和抗体反应，并保护小鼠免受致命病毒的攻击。在本研究中，我们从 E80 免疫小鼠中分离出 5 种 ZIKV 中和单克隆抗体 (mAb)。这五种单克隆抗体特异性结合并中和亚洲谱系寨卡病毒株。表位作图显示，所有五种 mAb 均识别位于 E 蛋白结构域 I 聚糖环上的新线性表位。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，这五种单克隆抗体形成了一类新的抗 ZIKV 抗体，对亚洲谱系 ZIKV 具有广谱中和作用。此类单克隆抗体的代表 5F8 被发现主要在病毒附着后进入过程的早期阶段发挥体外抑制功能。重要的是，mAb 5F8 能够为 ZIKV 致死感染小鼠模型提供全面保护。我们的结果对于开发抗 ZIKV 疫苗和治疗性单克隆抗体具有重要意义。