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Structural and functional analysis of protective antibodies targeting the threefold plateau of enterovirus 71
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Structural and functional analysis of protective antibodies targeting the threefold plateau of enterovirus 71
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Journal Article
Structural and functional analysis of protective antibodies targeting the threefold plateau of enterovirus 71
2020
Overview
Enterovirus 71 (EV71)-neutralizing antibodies correlate with protection and have potential as therapeutic agents. We isolate and characterize a panel of plasmablast-derived monoclonal antibodies from an infected child whose antibody response focuses on the plateau epitope near the icosahedral 3-fold axes. Eight of a total of 19 antibodies target this epitope and three of these potently neutralize the virus. Representative neutralizing antibodies 38-1-10A and 38-3-11A both confer effective protection against lethal EV71 challenge in hSCARB2-transgenic mice. The cryo-electron microscopy structures of the EV71 virion in complex with Fab fragments of these potent and protective antibodies reveal the details of a conserved epitope formed by residues in the BC and HI loops of VP2 and the BC and HI loops of VP3 spanning the region around the 3-fold axis. Remarkably, the two antibodies interact with the epitope in quite distinct ways. These plateau-binding antibodies provide templates for promising candidate therapeutics.
To date, no therapeutic agents against enterovirus 71, the causative agent of hand, foot and mouth disease, exist. Here, using Cryo-EM Huang et al. characterize two plasmablast-derived plateau-binding neutralizing antibodies conferring effective protection against lethal EV71 challenge in vivo.
Publisher
Nature Publishing Group UK,Nature Portfolio
Subject
/ Animals
/ Antibodies, Monoclonal - chemistry
/ Antibodies, Monoclonal - immunology
/ Antibodies, Neutralizing - chemistry
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - chemistry
/ Antibodies, Viral - immunology
/ Capsid Proteins - immunology
/ Enterovirus A, Human - chemistry
/ Enterovirus A, Human - genetics
/ Enterovirus A, Human - immunology
/ Enterovirus Infections - immunology
/ Enterovirus Infections - virology
/ Female
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mice
/ Science
