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 a nd dermal pathology in tropical regions. A vaccine directed to infective la rvae would provide a valuable control tool alongside the current methods of chemotherapy and vector control. Previously we have described the identifi cation of a chitinase cDNA that is expressed in a stage specific manner by O. volvulus infective third stage (L3) larvae. To evaluate its host protect ive potential, the complete open reading frame was cloned into the eukaryot ic expression plasmid pJW4303 and used to vaccinate mice by DNA immunisatio n with the Accell GeneGun. The survival of challenge infective larvae was m onitored using implanted micropore chambers. In the first trial, mice immun ised 3 times over 4 months with 1 mu g 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 mu g) and more frequent i mmunisations (5 times over 6 months) stimulated an IgG1 dominant response a nd a 53% reduction in parasite survival (p = 0.042). Antibodies from the va ccinated mice reacted with the cuticle of post-infective L3 larvae, implyin g that this may be the site of immune attack following secretion of chitina se. (C) 1999 Elsevier Science Ltd. All rights reserved.