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Structural and functional analysis of protective antibodies targeting the threefold plateau of enterovirus 71

DOI: 10.1038/s41467-020-19013-3 DOI Help

Authors: Kuan-Ying A. Huang (Chang Gung Memorial Hospital; Chang Gung University) , Daming Zhou (The Wellcome Centre for Human Genetics, University of Oxford) , Elizabeth E. Fry (The Wellcome Centre for Human Genetics, University of Oxford) , Abhay Kotecha (The Wellcome Centre for Human Genetics, University of Oxford) , Peng-Nien Huang (Chang Gung University) , Shu-Li Yang (Chang Gung University; Chang Gung Memorial Hospital) , Kuo-Chien Tsao (Chang Gung University; Chang Gung Memorial Hospital) , Yhu-Chering Huang (Chang Gung Memorial Hospital) , Tzou-Yien Lin (Chang Gung Memorial Hospital) , Jingshan Ren (The Wellcome Centre for Human Genetics, University of Oxford) , David I. Stuart (The Wellcome Centre for Human Genetics, University of Oxford; Diamond Light Source)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 11

State: Published (Approved)
Published: October 2020
Diamond Proposal Number(s): 10627

Open Access Open Access

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.

Journal Keywords: Cryoelectron microscopy; Viral infection; Virology; X-ray crystallography

Diamond Keywords: Viruses; Hand, Foot and Mouth Disease (HFMD)

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I03-Macromolecular Crystallography

Added On: 20/10/2020 09:24

Documents:
s41467-020-19013-3.pdf

Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Drug Discovery Infectious Diseases Pathogens Structural biology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)