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    Fasciola hepatica cathepsin L-like proteases: biology, function, and potential in the development of first generation liver fluke vaccines


    Dalton, John P. and O'Neill, Sandra M. and Stack, Colin M. and Collins, Peter R. and Walshe, Alan and Sekiya, Mary and Doyle, Sean and Mulcahy, Grace and Hoyle, Deborah and Khaznadji, Eric and Moire, Nathalie and Brennan, Gerard and Mousley, Angela and Kreshchenko, Natalia and Maule, Aaron G. and Donnelly, Sheila M. (2003) Fasciola hepatica cathepsin L-like proteases: biology, function, and potential in the development of first generation liver fluke vaccines. International Journal for Parasitology, 33 (11). pp. 1173-1181. ISSN 0020-7519

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    Abstract

    Fasciola hepatica secretes cathepsin L proteases that facilitate the penetration of the parasite through the tissues of its host, and also participate in functions such as feeding and immune evasion. The major proteases, cathepsin L1 (FheCL1) and cathepsin L2 (FheCL2) are members of a lineage that gave rise to the human cathepsin Ls, Ks and Ss, but while they exhibit similarities in their substrate specificities to these enzymes they differ in having a wider pH range for activity and an enhanced stability at neutral pH. There are presently 13 Fasciola cathepsin L cDNAs deposited in the public databases representing a gene family of at least seven distinct members, although the temporal and spatial expression of each of these members in the developmental stage of F. hepatica remains unclear. Immunolocalisation and in situ hybridisation studies, using antibody and DNA probes, respectively, show that the vast majority of cathepsin L gene expression is carried out in the epithelial cells lining the parasite gut. Within these cells the enzyme is packaged into secretory vesicles that release their contents into the gut lumen for the purpose of degrading ingested host tissue and blood. Liver flukes also express a novel multi-domain cystatin that may be involved in the regulation of cathepsin L activity. Vaccine trials in both sheep and cattle with purified native FheCL1 and FheCL2 have shown that these enzymes can induce protection, ranging from 33 to 79%, to experimental challenge with metacercariae of F. hepatica, and very potent anti-embryonation/hatch rate effects that would block parasite transmission. In this article we review the vaccine trials carried out over the past 8 years, the role of antibody and T cell responses in mediating protection and discuss the prospects of the cathepsin Ls in the development of first generation recombinant liver fluke vaccines.

    Item Type: Article
    Keywords: Helminths; Trematodes; Parasites; Cathepsins; Proteases; Vaccines; Immunology; Biochemistry;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 7404
    Identification Number: https://doi.org/10.1016/S0020-7519(03)00171-1
    Depositing User: Dr. Sean Doyle
    Date Deposited: 29 Aug 2016 15:29
    Journal or Publication Title: International Journal for Parasitology
    Publisher: Elsevier
    Refereed: Yes
    URI:

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