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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.

Original publication

DOI

10.1038/s41467-020-19013-3

Type

Journal article

Journal

Nature communications

Publication Date

16/10/2020

Volume

11

Addresses

Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan. arthur1726@cgmh.org.tw.

Keywords

Animals, Mice, Inbred C57BL, Humans, Mice, Enterovirus A, Human, Enterovirus Infections, Capsid Proteins, Antibodies, Monoclonal, Antibodies, Viral, Epitopes, Neutralization Tests, Female, Male, Antibodies, Neutralizing