Wu, Y., Egerton, G., Pappin, D. J., Harrison, R. A., Wilkinson, M. C., Underwood, A., Bianco, A. E. (April 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. Mol Biochem Parasitol, 134 (2). pp. 213-24. ISSN 0166-6851 (Print)0166-6851 (Linking)
Abstract
Onchocerca volvulus 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 (L3) 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 18kDa 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 Ov-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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Amino Acid Sequence Animals Antibodies, Helminth/blood/immunology Antigens, Helminth/immunology Base Sequence Brugia malayi/ genetics Cloning, Molecular Cross Reactions DNA, Helminth/chemistry/isolation & purification Genes, Helminth Helminth Proteins/chemistry/ genetics/ immunology/metabolism Humans Isoelectric Point Larva/immunology/metabolism/ultrastructure Mice Microscopy, Immunoelectron Molecular Sequence Data Molecular Weight Onchocerca volvulus/ genetics/growth & development/metabolism Onchocerciasis/immunology Sequence Alignment Sequence Analysis, Protein Sequence Homology Upper Gastrointestinal Tract/metabolism Vaccination |
| Subjects: | Investigative techniques and equipment Investigative techniques and equipment > spectroscopy > mass spectrometry Investigative techniques and equipment > spectroscopy |
| CSHL Authors: | |
| Communities: | CSHL labs > Pappin lab |
| Depositing User: | Matt Covey |
| Date: | April 2004 |
| Date Deposited: | 04 Mar 2013 21:25 |
| Last Modified: | 04 Mar 2013 21:25 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/27697 |
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