Fasciola hepatica Cathepsin L Zymogens: Immuno-Proteomic Evidence for Highly Immunogenic Zymogen-Specific Conformational Epitopes to Support Diagnostics Development

Clare Collett, Helen Phillips, Maggie Fisher, Sian Smith, Caroline Fenn, Phil Goodwin, Russ Morphew, Peter Brophy

Research output: Contribution to journalArticlepeer-review

4 Citations (SciVal)
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Abstract

Fasciola hepatica, the common liver fluke and causative agent of zoonotic fasciolosis, impacts on food security with global economic losses of over $3.2 BN per annum through deterioration of animal health, productivity losses, and livestock death and is also re-emerging as a foodborne human disease. Cathepsin proteases present a major vaccine and diagnostic target of the F. hepatica excretory/secretory (ES) proteome, but utilization in diagnostics of the highly antigenic zymogen stage of these proteins is surprisingly yet to be fully exploited. Following an immuno-proteomic investigation of recombinant and native procathepsins ((r)FhpCL1), including mass spectrometric analyses (DOI: 10.6019/PXD030293), and using counterpart polyclonal antibodies to a recombinant mutant procathepsin L (anti-rFhΔpCL1), we have confirmed recombinant and native cathepsin L zymogens contain conserved, highly antigenic epitopes that are conformationally dependent. Furthermore, using diagnostic platforms, including pilot serum and fecal antigen capture enzyme-linked immunosorbent assay (ELISA) tests, the diagnostic capacities of cathepsin L zymogens were assessed and validated, offering promising efficacy as markers of infection and for monitoring treatment efficacy.
Original languageEnglish
Pages (from-to)1997-2010
Number of pages14
JournalJournal of Proteome Research
Volume21
Issue number8
Early online date18 Jul 2022
DOIs
Publication statusPublished - 05 Aug 2022

Keywords

  • cathepsin
  • diagnostics
  • fasciolosis
  • recombinant
  • triclabendazole

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