DNA immunisation with Onchocerca volvulus chitinase induces partial protection against challenge infection with L3 larvae in mice.
The parasitic nematode, Onchocerca volvulus is a major cause of blindness and dermal pathology in tropical regions. A vaccine directed to infective larvae would provide a valuable control tool alongside the current methods of chemotherapy and vector control. Previously we have described the identification of a chitinase cDNA that is expressed in a stage specific manner by O. volvulus infective third stage (L3) larvae. To evaluate its host protective potential, the complete open reading frame was cloned into the eukaryotic expression plasmid pJW4303 and used to vaccinate mice by DNA immunisation with the Accell GeneGun. The survival of challenge infective larvae was monitored using implanted micropore chambers. In the first trial, mice immunised 3 times over 4 months with 1 microg O. volvulus chitinase DNA responded with modest antibody responses dominated by IgG2a and exhibited a 36% (p=0.189, NS) reduction in parasite survival compared with challenge controls. In the second trial, an increased dose of DNA (5 microg) and more frequent immunisations (5 times over 6 months) stimulated an IgG1 dominant response and a 53% reduction in parasite survival (p=0.042). Antibodies from the vaccinated mice reacted with the cuticle of post-infective L3 larvae, implying that this may be the site of immune attack following secretion of chitinase.
Harrison
R A
RA
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK. robharr@liverpool.ac.uk
Wu
Y
Y
Egerton
G
G
Bianco
A E
AE
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis / Q000097:blood; D000917:Antibody Formation / Q000276:immunology; D019470:Biolistics; D002417:Cattle; D002688:Chitinases / Q000235:genetics* / Q000276:immunology* / Q000648:ultrastructure; D018509:DNA, Helminth / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007814:Larva / Q000276:immunology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017181:Onchocerca volvulus / Q000201:enzymology* / Q000235:genetics / Q000276:immunology* / Q000648:ultrastructure; D009855:Onchocerciasis / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D012867:Skin / Q000378:metabolism; D015533:Transcriptional Activation / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*
D000909:Antibodies, Helminth; D018509:DNA, Helminth; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D002688:Chitinases