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.
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.)。
