Literature DB >> 15003841

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.

Yang Wu1, Gillian Egerton, Darryl J C Pappin, Robert A Harrison, Mark C Wilkinson, Anthony Underwood, Albert E Bianco.   

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.

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Year:  2004        PMID: 15003841     DOI: 10.1016/j.molbiopara.2003.12.002

Source DB:  PubMed          Journal:  Mol Biochem Parasitol        ISSN: 0166-6851            Impact factor:   1.759


  14 in total

1.  Filarial Abundant Larval Transcript Protein ALT-2: An Immunomodulatory Therapeutic Agent for Type 1 Diabetes.

Authors:  Sridhar M Reddy; Pooja M Reddy; Nitin Amdare; Vishal Khatri; Aaditya Tarnekar; Kalyan Goswami; Maryada Venkata Rami Reddy
Journal:  Indian J Clin Biochem       Date:  2016-06-07

Review 2.  A comprehensive, model-based review of vaccine and repeat infection trials for filariasis.

Authors:  C Paul Morris; Holly Evans; Sasha E Larsen; Edward Mitre
Journal:  Clin Microbiol Rev       Date:  2013-07       Impact factor: 26.132

3.  Immunogenicity of Brugia malayi Abundant Larval Transcript-2, a potential filarial vaccine candidate expressed in tobacco.

Authors:  Mathangi Ganapathy; Adhiseshan Perumal; Chakravarthi Mohan; Harunipriya Palaniswamy; Kaliraj Perumal
Journal:  Plant Cell Rep       Date:  2013-11-07       Impact factor: 4.570

4.  Molecular characterization and evaluation of Onchocerca volvulus-secreted larval acidic protein 1 (SLAP1) as a putative vaccine candidate on endemic population of lymphatic filariasis.

Authors:  Natarajan Mahalakshmi; Ramanathan Aparnaa; Lawrance Ansel Vishal; Perumal Kaliraj
Journal:  Parasitol Res       Date:  2013-07-05       Impact factor: 2.289

5.  Crucial epitopes of Wuchereria bancrofti abundant larval transcript recognized in natural infection.

Authors:  J Madhumathi; D Pradiba; P R Prince; P J Jeyaprita; D N Rao; P Kaliraj
Journal:  Eur J Clin Microbiol Infect Dis       Date:  2010-08-29       Impact factor: 3.267

6.  The Onchocerca volvulus cysteine proteinase inhibitor, Ov-CPI-2, is a target of protective antibody response that increases with age.

Authors:  Fidelis Cho-Ngwa; Jing Liu; Sara Lustigman
Journal:  PLoS Negl Trop Dis       Date:  2010-08-24

7.  Proteomic analysis of secretory products from the model gastrointestinal nematode Heligmosomoides polygyrus reveals dominance of venom allergen-like (VAL) proteins.

Authors:  James P Hewitson; Yvonne Harcus; Janice Murray; Maaike van Agtmaal; Kara J Filbey; John R Grainger; Stephen Bridgett; Mark L Blaxter; Peter D Ashton; David A Ashford; Rachel S Curwen; R Alan Wilson; Adam A Dowle; Rick M Maizels
Journal:  J Proteomics       Date:  2011-06-29       Impact factor: 4.044

Review 8.  Helminth immunoregulation: the role of parasite secreted proteins in modulating host immunity.

Authors:  James P Hewitson; John R Grainger; Rick M Maizels
Journal:  Mol Biochem Parasitol       Date:  2009-05-03       Impact factor: 1.759

9.  Immunisation with a multivalent, subunit vaccine reduces patent infection in a natural bovine model of onchocerciasis during intense field exposure.

Authors:  Benjamin L Makepeace; Siv Aina Jensen; Sandra J Laney; Charles K Nfon; Leo M Njongmeta; Vincent N Tanya; Steven A Williams; Albert E Bianco; Alexander J Trees
Journal:  PLoS Negl Trop Dis       Date:  2009-11-10

10.  Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes.

Authors:  Simon A Babayan; Honglin Luo; Nick Gray; David W Taylor; Judith E Allen
Journal:  PLoS Negl Trop Dis       Date:  2012-12-27
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