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

PLoS Pathog. 2021 Apr 28;17(4):e1009507. doi: 10.1371/journal.ppat.1009507. eCollection 2021 Apr.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • Antigenic Variation
  • Capsid / immunology
  • Cattle
  • Cryoelectron Microscopy / veterinary
  • Epitopes / immunology
  • Foot-and-Mouth Disease / virology*
  • Foot-and-Mouth Disease Virus / immunology*
  • Foot-and-Mouth Disease Virus / ultrastructure
  • Serogroup

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes

Grants and funding

This work was supported by the National Program on Key Research Project of China [(2020YFA0707500, to Z.L.), (2017YFC0840300, to Z.R.), (2016YFD0501500, to Z. Liu)] and the National Natural Science Foundation of China (NSFC) [(31902288, to K.L.), (32072873, to Y.C.)]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.