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<p>Foot-and-mouth disease virus (FMDV) causes a devastating disease that threatens global food security. Vaccination is hindered by antigenic diversity across serotypes. To identify cross-serotype neutralising epitopes, we isolated 24 FMDV-specific antibodies from cattle sequentially vaccinated with antigens from four serotypes, of which three neutralised three vaccine strains. These three antibodies neutralised 21 and bound 59 additional topotypes across O, A, Asia 1, and C serotypes. Cryo-EM complexes of Fabs with FMD virus-like particles indicated all three recognise a common flexible epitope at the VP1 C-terminus, confirmed by binding competition. Crystallography and structural modelling revealed that a normally inaccessible surface of the hydrophobic VP1 C-terminal peptides inserts into a similar groove in all three antibodies. Comparison of neutralisation activity and integrin receptor blocking by whole antibodies, F(ab’)<sub>2</sub>s, and Fabs suggests neutralisation is mediated by Fc steric hindrance of receptor binding. This cryptic, linear, and cross-serotype neutralising epitope may inform improved FMD vaccines.</p>

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Cattle antibodies identify a cross-serotype broadly neutralising foot-and-mouth disease virus epitope

  • 期刊论文

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  • 发表日期：

    2026年4月2日

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  • Marie Bonnet-Di Placido,
  • Helen M. E. Duyvesteyn,
  • Angela W. Steyn,
  • Abigail L. Hay,
  • Claudine Porta,
  • Kristel Ramirez Valdez,
  • Elena Lokhman,
  • Sylvia Crossley,
  • Kevan Hanson,
  • William N. Mwangi,
  • Danish Munir,
  • Eva Perez-Martin,
  • Nick J. Knowles,
  • Alison Burman,
  • Abdelaziz A. Yassin,
  • Amin Asfor,
  • Cristina Faralla,
  • Katherine J. Lam,
  • Róisín McComb,
  • Carina Leifeld,
  • Kimberly Pietersz,
  • Donald P. King,
  • Erwin van den Born,
  • Sherie K. Duncan,
  • Bryan Charleston,
  • Elizabeth E. Fry,
  • Jingshan Ren,
  • David I. Stuart,
  • John A. Hammond

摘要

Foot-and-mouth disease virus (FMDV) causes a devastating disease that threatens global food security. Vaccination is hindered by antigenic diversity across serotypes. To identify cross-serotype neutralising epitopes, we isolated 24 FMDV-specific antibodies from cattle sequentially vaccinated with antigens from four serotypes, of which three neutralised three vaccine strains. These three antibodies neutralised 21 and bound 59 additional topotypes across O, A, Asia 1, and C serotypes. Cryo-EM complexes of Fabs with FMD virus-like particles indicated all three recognise a common flexible epitope at the VP1 C-terminus, confirmed by binding competition. Crystallography and structural modelling revealed that a normally inaccessible surface of the hydrophobic VP1 C-terminal peptides inserts into a similar groove in all three antibodies. Comparison of neutralisation activity and integrin receptor blocking by whole antibodies, F(ab’)2s, and Fabs suggests neutralisation is mediated by Fc steric hindrance of receptor binding. This cryptic, linear, and cross-serotype neutralising epitope may inform improved FMD vaccines.