@article{497a12fb63d6459a818e0d02c43367a3,
title = "Structural and functional analysis of protective antibodies targeting the threefold plateau of enterovirus 71",
abstract = "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.",
author = "Huang, {Kuan Ying A.} and Daming Zhou and Fry, {Elizabeth E.} and Abhay Kotecha and Huang, {Peng Nien} and Yang, {Shu Li} and Tsao, {Kuo Chien} and Huang, {Yhu Chering} and Lin, {Tzou Yien} and Jingshan Ren and Stuart, {David I.}",
note = "Funding Information: We acknowledge the BD FACSAriaTM cell sorter service provided by the Core Instrument Center of Chang Gung University. These studies were funded by the Chang Gung Medical Research Program (CMRPG3E1471-3, CORPG3J0111). The authors would like to thank Diamond Light Source for beamtime (proposal MX10627), and the staff of beamlines I03 and for assistance with crystal testing and data collection. D.Z. is supported by a China Scholarship Council-University of Oxford Scholarship, J.R. by the Wellcome Trust (101122/Z/13/Z) and D.I.S. and E.E.F. by the UK Medical Research Council (MR/N00065X/1). This is a contribution from the UK Instruct-ERIC Centre. The Wellcome Centre for Human Genetics is supported by the Wellcome Trust (grant 090532/Z/09/Z). Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-020-19013-3",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}