Structures of Foot-and-mouth Disease Virus with neutralizing antibodies derived from recovered natural host reveal a mechanism for cross-serotype neutralization

• Published in: PLoS pathogens Vol. 17; no. 4; p. e1009507
• Main Authors: He, Yong, Li, Kun, Cao, Yimei, Sun, Zixian, Li, Pinghua, Bao, Huifang, Wang, Sheng, Zhu, Guoqiang, Bai, Xingwen, Sun, Pu, Liu, Xuerong, Yang, Cheng, Liu, Zaixin, Lu, Zengjun, Rao, Zihe, Lou, Zhiyong
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2021; Public Library of Science (PLoS)
• Subjects: Amino acids; Analysis; Antibodies; Antigenic determinants; Baits; Biology and Life Sciences; Cross-reactivity; Epidemics; Flow cytometry; Fluorescence; Foot & mouth disease; Foot-and-mouth disease virus; Health aspects; Identification and classification; Immunoglobulin G; Immunoglobulin M; Immunological memory; Lymphocytes B; Medicine and Health Sciences; Memory cells; Neutralization; Neutralization (Chemistry); Research and Analysis Methods; RNA viruses; Strains (organisms); Structure; Vaccines; Viral antibodies; Viruses; China; Tibet; Asia
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1009507

The development of a universal vaccine against foot-and-mouth disease virus (FMDV) is hindered by cross-serotype antigenic diversity and by a lack of knowledge regarding neutralization of the virus in natural hosts. In this study, we isolated serotype O-specific neutralizing antibodies (NAbs) (F145 and B77) from recovered natural bovine hosts by using the single B cell antibody isolation technique. We also identified a serotype O/A cross-reacting NAb (R50) and determined virus-NAb complex structures by cryo-electron microscopy at near-atomic resolution. F145 and B77 were shown to engage the capsid of FMDV-O near the icosahedral threefold axis, binding to the BC/HI-loop of VP2. In contrast, R50 engages the capsids of both FMDV-O and FMDV-A between the 2- and 5-fold axes and binds to the BC/EF/GH-loop of VP1 and to the GH-loop of VP3 from two adjacent protomers, revealing a previously unknown antigenic site. The cross-serotype neutralizing epitope recognized by R50 is highly conserved among serotype O/A. These findings help to elucidate FMDV neutralization by natural hosts and provide epitope information for the development of a universal vaccine for cross-serotype protection against FMDV.