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TitleStructural and functional analysis of protective antibodies targeting the threefold plateau of enterovirus 71.
Journal, issue, pagesNat Commun, Vol. 11, Issue 1, Page 5253, Year 2020
Publish dateOct 16, 2020
AuthorsKuan-Ying A Huang / Daming Zhou / Elizabeth E Fry / Abhay Kotecha / Peng-Nien Huang / Shu-Li Yang / Kuo-Chien Tsao / Yhu-Chering Huang / Tzou-Yien Lin / Jingshan Ren / David I Stuart /
PubMed AbstractEnterovirus 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 ...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.
External linksNat Commun / PubMed:33067459 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.7 - 2.8 Å
Structure data

11061

6z3p

EMDB-11061, PDB-6z3p:
Structure of EV71 in complex with a protective antibody 38-3-11A Fab
Method: EM (single particle) / Resolution: 2.8 Å

11062

6z3q

EMDB-11062, PDB-6z3q:
Structure of EV71 in complex with a protective antibody 38-1-10A Fab
Method: EM (single particle) / Resolution: 2.7 Å

PDB-6z3k:
Structure of protective antibody 38-1-10A Fab
Method: X-RAY DIFFRACTION / Resolution: 2.7 Å

Chemicals

ChemComp-EDO:
1,2-ETHANEDIOL / Ethylene glycol

ChemComp-HOH:
WATER / Water

ChemComp-SPH:
SPHINGOSINE / Sphingosine

Source
  • enterovirus a71
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM / EV71 / antibody 38-3-11A / antibody 38-1-10A / EV71-Fab complex / VIRUS

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