针对寨卡病毒包膜蛋白结构域III线性表位的中和抗体的研发

Development of a neutralizing antibody targeting linear epitope of the envelope protein domain III of ZIKV.

作者信息

Hu Huan, Liu Rongfei, Li Qianlin, Wang Jin, Deng Qiang, Lu YuYing, Wu Qin, Chen Zeliang, Lu Jiahai

机构信息

School of Public Health, Sun Yat-Sen University, Guangzhou, Guangdong Province, China; One Health Center of Excellence for Research & Training, Sun Yat-Sen University, Guangzhou, Guangdong Province 510080, China.

出版信息

Virus Res. 2021 Dec;306:198601. doi: 10.1016/j.virusres.2021.198601. Epub 2021 Oct 20.

DOI:10.1016/j.virusres.2021.198601

PMID:34678322

Abstract

Zika virus (ZIKV) infection represents an emerging infectious disease that poses an increasing threat to human health, especially after the ZIKV outbreak in Brazil in 2015. Unfortunately, there continues to be a lack of highly effective antiviral drugs or vaccines against ZIKV. In this study, we expressed the ZIKV envelope protein domain III (ZIKV EDIII) in E. coli strain BL21. The purified recombinant protein was used to immunize mice to produce monoclonal antibodies (mAbs). After 6 screening and 5 subcloning cycles, 10 monoclonal cell lines that stably produced antibodies, termed 2F5, 5B8, 6G6, 7E12, 8B6, 17E6, 19E7, 20F4, 26G6, and 37E6, were identified. The mAb 8B6 could neutralize ZIKV and recognize the ZIKV EDIII epitope (GRLITANPVITESTE). Another 9 mAbs did not exhibit neutralizing activity; however, they could specifically recognize the ZIKV EDIII and ZIKV lysate, suggesting their potential use in the diagnosis of ZIKV.

摘要

寨卡病毒（ZIKV）感染是一种新出现的传染病，对人类健康构成越来越大的威胁，尤其是在2015年巴西爆发寨卡病毒疫情之后。不幸的是，目前仍然缺乏针对寨卡病毒的高效抗病毒药物或疫苗。在本研究中，我们在大肠杆菌BL21菌株中表达了寨卡病毒包膜蛋白结构域III（ZIKV EDIII）。纯化的重组蛋白用于免疫小鼠以产生单克隆抗体（mAb）。经过6轮筛选和5轮亚克隆，鉴定出10个稳定产生抗体的单克隆细胞系，分别命名为2F5、5B8、6G6、7E12、8B6、17E6、19E7、20F4、26G6和37E6。单克隆抗体8B6能够中和寨卡病毒并识别寨卡病毒EDIII表位（GRLITANPVITESTE）。另外9种单克隆抗体不具有中和活性；然而，它们能够特异性识别寨卡病毒EDIII和寨卡病毒裂解物，表明它们在寨卡病毒诊断中的潜在用途。