https://scholars.lib.ntu.edu.tw/handle/123456789/630620
Title: | Structural and functional analysis of protective antibodies targeting the threefold plateau of enterovirus 71 | Authors: | Kuan-Ying A. Huang Zhou, Daming Fry, Elizabeth E. Kotecha, Abhay Huang, Peng Nien Yang, Shu Li Tsao, Kuo Chien Huang, Yhu Chering Lin, Tzou Yien Ren, Jingshan Stuart, David I. |
Keywords: | NANOLITRE CRYSTALLIZATION EXPERIMENTS; NEUTRALIZING ANTIBODIES; INFECTION; ATTACHMENT; PARTICLES; MECHANISM; CHILDREN; RECEPTOR; DESIGN; SYSTEM | Issue Date: | 16-Oct-2020 | Publisher: | NATURE RESEARCH | Journal Volume: | 11 | Journal Issue: | 1 | Start page/Pages: | 5253 | Source: | Nature Communications | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/630620 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-020-19013-3 |
Appears in Collections: | 免疫學研究所 |
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s41467-020-19013-3.pdf | Structural and functional analysis of protective antibodies targeting the threefold plateau of enterovirus 71 | 3.57 MB | Adobe PDF | View/Open |
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