Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA, U.K.
Ridgeway Research Ltd., Park Farm Buildings, Park Lane, St. Briavels, Gloucestershire GL15 6QX, U.K.
J Proteome Res. 2022 Aug 5;21(8):1997-2010. doi: 10.1021/acs.jproteome.2c00299. Epub 2022 Jul 18.
, 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 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.
肝片吸虫是一种常见的肝吸虫，也是人畜共患片形吸虫病的病原体，它通过损害动物健康、降低生产力、导致牲畜死亡，对全球食品安全造成每年超过 32 亿美元的经济损失，而且它作为食源性人类疾病也正在重新出现。组织蛋白酶蛋白酶是排泄/分泌（ES）蛋白质组的主要疫苗和诊断靶标，但令人惊讶的是，这些蛋白质的高度抗原性酶原阶段在诊断中的利用尚未得到充分开发。在对重组和天然原组织蛋白酶（（r）FhpCL1）进行免疫蛋白质组学研究后，包括质谱分析（DOI：10.6019/PXD030293），并使用针对重组突变原组织蛋白酶 L 的相应多克隆抗体（抗-rFhΔpCL1），我们已经证实重组和天然组织蛋白酶 L 酶原含有保守的、高度抗原性的表位，这些表位依赖于构象。此外，使用包括初步血清和粪便抗原捕获酶联免疫吸附试验（ELISA）测试在内的诊断平台，评估和验证了组织蛋白酶 L 酶原的诊断能力，为感染标志物和监测治疗效果提供了有前景的功效。
