Qu Panke, Zhang Chao, Li Min, Ma Weimin, Xiong Pei, Liu Qingwei, Zou Gang, Lavillette Dimitri, Yin Feifei, Jin Xia, Huang Zhong
1CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Center for Biosafety Mega-Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031 China.
2Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, Hainan, 571101 China.
Cell Discov. 2020 Feb 4;6:5. doi: 10.1038/s41421-019-0140-8. eCollection 2020.
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.
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的获批疫苗或治疗药物。我们之前已表明，重组ZIKV E80蛋白可诱导强效中和抗体反应，并保护小鼠免受致命性病毒攻击。在本研究中，我们从经E80免疫的小鼠中分离出5种ZIKV中和单克隆抗体（mAb）。这5种mAb特异性结合并中和亚洲谱系ZIKV毒株。表位作图显示，所有这5种mAb均识别位于E蛋白结构域I糖基环上的一个新型线性表位。序列比对显示，该表位在ZIKV中极为保守，但在ZIKV与其他黄病毒之间高度可变。因此，这5种mAb形成了一类新的抗ZIKV抗体，对亚洲谱系ZIKV表现出广谱中和作用。发现该mAb类别的一个代表5F8在体外主要在病毒附着后进入过程的早期发挥抑制功能。重要的是，mAb 5F8能够在ZIKV致死性感染的小鼠模型中提供完全保护。我们的结果对开发抗ZIKV疫苗和治疗性mAb具有重要意义。
