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The Secreted Larval Acidic Proteins (SLAPs) of Onchocerca spp. are encoded by orthologues of the alt gene family of Brugia malayi and have host protective potential

Wu, Yang, Egerton, Gillian, Pappin, D. J. C., Harrison, Robert, Wilkinson, M. C., Underwood, A. and Bianco, Albert E. (2004) 'The Secreted Larval Acidic Proteins (SLAPs) of Onchocerca spp. are encoded by orthologues of the alt gene family of Brugia malayi and have host protective potential'. Molecular and Biochemical Parasitology, Vol 134, Issue 2, pp. 213-224.

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Abstract

Onchocerca volvilus is a tissue-dwelling, vector-borne nematode parasite of humans and the causative agent of onchocerciasis, or 'River Blindness'. Resistance to infection is associated with immune responses to the infective, third-stage (1-3) larvae. The antigens of greatest interest for their vaccine potential are surface and secreted molecules. We have previously identified a family of Secreted Larval Acidic Proteins (SLAPs) from the L3 larvae of O. volvulus by biosynthetic labelling. Here, we provide further characterisation of these molecules following cloning and expression of the corresponding cDNAs. Using protein sequencing, we show that SLAPs are members of the alt gene family. first described in the lymphatic filarial parasite, Brugia malayi. Ov-ALT-1 and Ov-ALT-2 correspond with 20 and 18 kDa SLAPs. Both proteins are highly acidic and related by sequence, differing chiefly in an 8-amino acid deletion from Ov-ALT-2. By immunochemistry, we confirm that 0v-ALTs are highly stage-specific, being expressed exclusively in late L2 and L3 larvae during growth in the vector. They are synthesised and stored in the glandular oesophagus. Secretion is triggered by the resumption of development in the definitive host and occurs via the pseudocoelom and cuticle. Serological responses in humans to recombinant Ov-ALT-1 indicate that the level of IgG production may be governed by the force of transmission but does not overtly reflect infection status. Immunisation of mice with recombinant Ov-ALT-1 resulted in a modest level of protection against challenge with O. volvulus L3 larvae (P = 0.036). We conclude that Ov-ALT genes, like those of other filariae, are of interest from the standpoint of parasite transmission and infectivity. They may also offer promise as components of a future sub-unit vaccine should the means to enhance protection be achieved. (C) 2003 Published by Elsevier B.V.

Item Type: Article
Uncontrolled Keywords: onchocerca volvulus l3-specificity glandular oesophagus secretion abundant larval transcript (alt) secreted larval acidic protein (slap) vaccination acanthocheilonema-viteae caenorhabditis-elegans polyacrylamide-gels filarial parasite escherichia-coli infective larvae volvulus stage expression antigens
Subjects: QU Biochemistry > Genetics > QU 450 General Works
QX Parasitology > Helminths. Annelida > QX 301 Filarioidea
QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 850 Nematode infections (General)
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1016/j.molbiopara.2003.12.002
Depositing User: Sarah Lewis-Newton
Date Deposited: 30 May 2012 14:34
Last Modified: 06 Feb 2018 13:03
URI: http://archive.lstmed.ac.uk/id/eprint/2204

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