Structural insights into the distinct protective mechanisms of human antibodies targeting ZIKV NS1  

作　　者：Qi Pan Xiaomin Xing Jianhai Yu Qiang Chen Haizhan Jiao Wanqin Zhang Yingfen Wen Ming Gao Wei Zhao Lei Yu Hongli Hu 

机构地区：[1]Kobilka Institute of Innovative Drug Discovery,School of Medicine,The Chinese University of Hong Kong,Shenzhen,Guangdong,China [2]Guangzhou Eighth People’s Hospital,Guangzhou Medical University,Guangdong,China [3]BSL-3 Laboratory(Guangdong),Guangdong Provincial Key Laboratory of Tropical Disease Research,School of Public Health,Southern Medical University,Guangdong,China

出　　处：《hLife》2024年第10期527-541,共15页健康科学（英文）

基　　金：supported by grants from the National Natural Science Foundation of China(81971924 to L.Y.and 32370146 to W.Z.);Guangzhou Municipal Science and Technology Bureau(2023A03J0791 to L.Y.);Guangdong Science and Technology Program(2021B1212030014 to W.Z.);Guangdong Basic and Applied Basic Research Fund Enterprise Joint Fund(2021A1515220017 to W.Z.);Medical Scientific Research Foundation of Guangdong Province(B2022112 to J.Y.),Shenzhen Science and Technology Innovation Committee(JCYJ20210324131802008 to H.H.);Ganghong Young Scholar Development Fund(to H.H.);the Shenzhen-Hong Kong Cooperation Zone for Technology and Innovation(HZQB-KCZYB-2020056 to H.H.);the Kobilka Institute of Innovative Drug Discovery and Presidential Fellowship and University Development Fund at the Chinese University of Hong Kong,Shenzhen(to H.H.,H.J.,and Q.C.);Presidential Fellowship at the Chinese University of Hong Kong,Shenzhen(to Q.P.and W.Z.)。

摘　　要：Antibodies targeting non-structural protein 1(NS1)confer protection against Zika virus(ZIKV).Although monoclonal an-tibodies(MAbs)3G2 and 4B8 are more potent than MAb 4F10 in suppressing ZIKV infection in neonatal mice models,the epitopes are unclear.Herein,we determined the Cryo-electron microscopy(Cryo-EM)structures of ZIKV NS1 in com-plex withfive human antibodies at 2.6–2.9Åresolution.Group I antibodies(3G2 and 4B8)recognize the previously un-reported epitopes on the outer surface of the NS1 dimer.The unique binding mode of Group I antibodies led to a stronger recognition of the cell surface form of NS1 and completely inhibited secreted form non-structural protein 1(sNS1)-induced endothelial permeability via their immunoglobulin G(IgG)and Fab.Group II antibodies(4F10,2E11,and 14G5)recognize common epitopes in the distal end of the b-ladder domain,with a blockade efficiency that may be related to their affinity for the sNS1 protein and the presence of full-length IgG.Thesefindings elucidate the correlation between epitope recognition and protective efficacy of anti-NS1 antibodies and highlight the diagnostic and therapeutic potential of 3G2 and 4B8.

关 键 词：Zika virus(ZIKV) non-structural protein 1(NS1) monoclonal antibodies(MAbs) EPITOPES 

分 类 号：R392[医药卫生—免疫学]