A broadly reactive ultralong bovine antibody that can determine the integrity of foot-and-mouth disease virus capsids.

Autor: Clarke JD; The Division of Structural Biology, Nuffield Department of Medicine, The Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.; The Pirbright Institute, Woking, GU24 0NF, UK.; Diamond Light Source, Didcot, OX11 0DE, UK.; Present address: Structural Biology, The Rosalind Franklin Institute, Didcot, OX11 0QX, UK., Duyvesteyn HME; The Division of Structural Biology, Nuffield Department of Medicine, The Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK., Perez-Martin E; The Pirbright Institute, Woking, GU24 0NF, UK., Latišenko U; MSD Animal Health, 5831 AN Boxmeer, Netherlands., Porta C; The Division of Structural Biology, Nuffield Department of Medicine, The Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK., Humphreys KV; The Pirbright Institute, Woking, GU24 0NF, UK., Hay AL; The Pirbright Institute, Woking, GU24 0NF, UK., Ren J; The Division of Structural Biology, Nuffield Department of Medicine, The Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK., Fry EE; The Division of Structural Biology, Nuffield Department of Medicine, The Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK., van den Born E; MSD Animal Health, 5831 AN Boxmeer, Netherlands., Charleston B; The Pirbright Institute, Woking, GU24 0NF, UK., Bonnet-Di Placido M; The Pirbright Institute, Woking, GU24 0NF, UK., Owens RJ; The Division of Structural Biology, Nuffield Department of Medicine, The Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.; Structural Biology, The Rosalind Franklin Institute, Didcot, OX11 0QX, UK., Stuart DI; The Division of Structural Biology, Nuffield Department of Medicine, The Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.; Diamond Light Source, Didcot, OX11 0DE, UK.; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, OX3 7BN, UK., Hammond JA; The Pirbright Institute, Woking, GU24 0NF, UK.
Jazyk: angličtina
Zdroj: The Journal of general virology [J Gen Virol] 2024 Oct; Vol. 105 (10).
DOI: 10.1099/jgv.0.002032
Abstrakt: 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.
Databáze: MEDLINE