A broadly reactive ultralong bovine antibody that can determine the integrity of foot-and-mouth disease virus capsids
Foot-and-mouth disease vaccination using inactivated virus is suboptimal, as the icosahedral viral capsids often disassemble into antigenically distinct pentameric units during long-term storage, or exposure to elevated temperature or lowered pH, and thus raise a response that is no longer protective. Furthermore, as foot-and-mouth disease virus (FMDV)'s seven serotypes are antigenically diverse, cross-protection from a single serotype vaccine is limited, and most existing mouse and bovine antibodies and camelid single-domain heavy chain-only antibodies are serotype-specific. For quality control purposes, there is a real need for pan-serotype antibodies that clearly distinguish between pentamer (12S) and protective intact FMDV capsid. To date, few cross-serotype bovine-derived antibodies have been reported in the literature. We identify a bovine antibody with an ultralong CDR-H3, Ab117, whose structural analysis reveals that it binds to a deep, hydrophobic pocket on the interior surface of the capsid via the CDR-H3. Main-chain and hydrophobic interactions provide broad serotype specificity. ELISA analysis confirms that Ab117 is a novel pan-serotype and conformational epitope-specific 12S reagent, suitable for assessing capsid integrity.
Authors
- Eva Pérez-Martín (ORCID: https://orcid.org/0000-0002-4355-4367)
- Raymond J. Owens (ORCID: https://orcid.org/0000-0002-3705-2993)
- Helen M. E. Duyvesteyn (ORCID: https://orcid.org/0000-0002-4641-5442)
- Marie Bonnet‐Di Placido (ORCID: https://orcid.org/0000-0002-8299-5595)
- Erwin van den Born (ORCID: https://orcid.org/0000-0002-0341-2874)
- Kirsty M. Humphreys
- Bryan Charleston (ORCID: https://orcid.org/0000-0002-6952-9338)
- David I. Stuart (ORCID: https://orcid.org/0000-0002-3426-4210)
- Abigail L. Hay (ORCID: https://orcid.org/0000-0002-8143-2109)
- Jingshan Ren (ORCID: https://orcid.org/0000-0003-4015-1404)
- John A. Hammond (ORCID: https://orcid.org/0000-0002-2213-3248)
- Elizabeth E. Fry (ORCID: https://orcid.org/0000-0001-9754-5303)
- John Clarke (ORCID: https://orcid.org/0000-0001-7891-7626)
- Claudine Porta (ORCID: https://orcid.org/0000-0002-6788-4141)
- Undīne Latišenko
Institutions
- The Pirbright Institute (GB)
- Centre for Human Genetics (GB)
- Diamond Light Source (GB)
- University of Oxford (GB)
- Rosalind Franklin Institute (GB)
- MSD (Netherlands) (NL)
Publication Details
- Journal
- Journal of General Virology
- Published
- 2024-10-18
- DOI
- https://doi.org/10.1099/jgv.0.002032
- Citations
- 5
- Primary Topic
- Animal Disease Management and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 2.84
Funders
- Bill and Melinda Gates Foundation
- Wellcome Trust
- UK Research and Innovation
- National Institute for Health and Care Research
- Directorate for Biological Sciences
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Biotechnology and Biological Sciences Research Council
- Biomedical Research Council
- NIHR Oxford Biomedical Research Centre