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.
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.
Division of Molecular Biology and Immunology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK. ywu@liverpool.ac.uk
Yang
Y
Wu
Gillian
G
Egerton
Darryl J C
DJ
Pappin
Robert A
RA
Harrison
Mark C
MC
Wilkinson
Anthony
A
Underwood
Albert E
AE
Bianco
D000595:Amino Acid Sequence; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood / Q000276:immunology; D000947:Antigens, Helminth / Q000276:immunology; D001483:Base Sequence; D017178:Brugia malayi / Q000235:genetics*; D003001:Cloning, Molecular; D003429:Cross Reactions; D018509:DNA, Helminth / Q000737:chemistry / Q000302:isolation & purification; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007526:Isoelectric Point; D007814:Larva / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D008970:Molecular Weight; D017181:Onchocerca volvulus / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D009855:Onchocerciasis / Q000276:immunology; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D017385:Sequence Homology; D041742:Upper Gastrointestinal Tract / Q000378:metabolism; D014611:Vaccination
C117003:ALT-1 protein, Onchocerca volvulus; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D018509:DNA, Helminth; D015801:Helminth Proteins