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

Dalton, JP; Neill, SO; Stack, C; Collins, P; Walshe, A; Sekiya, M; Doyle, S; Mulcahy, G; Hoyle, D; Khaznadji, E; Moiré, N; Brennan, G; Mousley, A; Kreshchenko, N; Maule, AG; Donnelly, SM

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

Dalton, JP Neill, SO Stack, C Collins, P Walshe, A Sekiya, M Doyle, S Mulcahy, G Hoyle, D Khaznadji, E Moiré, N Brennan, G Mousley, A Kreshchenko, N Maule, AG Donnelly, SM

Permalink

Publication Type:: Journal Article
Citation:: International Journal for Parasitology, 2003, 33 (11), pp. 1173 - 1181
Issue Date:: 2003-09-30

Closed Access

	Filename	Description	Size
	2006012450OK.pdf		394.69 kB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	Dalton, JP	en_US
dc.contributor.author	Neill, SO	en_US
dc.contributor.author	Stack, C	en_US
dc.contributor.author	Collins, P	en_US
dc.contributor.author	Walshe, A	en_US
dc.contributor.author	Sekiya, M	en_US
dc.contributor.author	Doyle, S	en_US
dc.contributor.author	Mulcahy, G	en_US
dc.contributor.author	Hoyle, D	en_US
dc.contributor.author	Khaznadji, E	en_US
dc.contributor.author	Moiré, N	en_US
dc.contributor.author	Brennan, G	en_US
dc.contributor.author	Mousley, A	en_US
dc.contributor.author	Kreshchenko, N	en_US
dc.contributor.author	Maule, AG	en_US
dc.contributor.author	Donnelly, SM https://orcid.org/0000-0003-2005-3698	en_US
dc.date.issued	2003-09-30	en_US
dc.identifier.citation	International Journal for Parasitology, 2003, 33 (11), pp. 1173 - 1181	en_US
dc.identifier.issn	0020-7519	en_US
dc.identifier.uri	http://hdl.handle.net/10453/8903
dc.description.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. © 2003 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.	en_US
dc.relation.ispartof	International Journal for Parasitology	en_US
dc.relation.isbasedon	10.1016/S0020-7519(03)00171-1	en_US
dc.subject.classification	Mycology & Parasitology	en_US
dc.subject.mesh	Intestines	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Cattle	en_US
dc.subject.mesh	Sheep	en_US
dc.subject.mesh	Fasciola hepatica	en_US
dc.subject.mesh	Fascioliasis	en_US
dc.subject.mesh	Cattle Diseases	en_US
dc.subject.mesh	Sheep Diseases	en_US
dc.subject.mesh	Cathepsins	en_US
dc.subject.mesh	Cysteine Endopeptidases	en_US
dc.subject.mesh	Vaccines	en_US
dc.subject.mesh	Antigens, Helminth	en_US
dc.subject.mesh	Gene Expression	en_US
dc.subject.mesh	Host-Parasite Interactions	en_US
dc.subject.mesh	Cathepsin L	en_US
dc.title	Fasciola hepatica cathepsin L-like proteases: Biology, function, and potential in the development of first generation liver fluke vaccines	en_US
dc.type	Journal Article
utslib.citation.volume	11	en_US
utslib.citation.volume	33	en_US
utslib.for	0707 Veterinary Sciences	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	0608 Zoology	en_US
dc.location.activity	ISI:000221022400037
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	11	en_US
pubs.publication-status	Published	en_US
pubs.volume	33	en_US

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. © 2003 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/8903