Structural and functional analysis of protective antibodies targeting the threefold plateau of enterovirus 71.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 10 2020
16 10 2020
Historique:
received:
11
03
2020
accepted:
17
09
2020
entrez:
17
10
2020
pubmed:
18
10
2020
medline:
18
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33067459
doi: 10.1038/s41467-020-19013-3
pii: 10.1038/s41467-020-19013-3
pmc: PMC7567869
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Capsid Proteins
0
Epitopes
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5253Subventions
Organisme : Medical Research Council
ID : MR/N00065X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V001329/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 090532/Z/09/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 101122/Z/13/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
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