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

Authors :
Huang KA
Zhou D
Fry EE
Kotecha A
Huang PN
Yang SL
Tsao KC
Huang YC
Lin TY
Ren J
Stuart DI
Source :
Nature communications [Nat Commun] 2020 Oct 16; Vol. 11 (1), pp. 5253. Date of Electronic Publication: 2020 Oct 16.
Publication Year :
2020

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.

Details

Language :
English
ISSN :
2041-1723
Volume :
11
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
33067459
Full Text :
https://doi.org/10.1038/s41467-020-19013-3