In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination

• Published in: Proceedings of the National Academy of Sciences - PNAS 2006-04, Vol.103 (15), p.5971-5976
• Main Authors: Tchakoute, V.L, Graham, S.P, Jensen, S.A, Makepeace, B.L, Nfon, C.K, Njongmeta, L.M, Lustigman, S, Enyong, P.A, Tanya, V.N, Bianco, A.E
• Format: Article
• Language: English
• Subjects: adult worm burden; animal models; Animals; Anthelmintics - therapeutic use; Biological Sciences; Cattle; cattle diseases; Cattle Diseases - drug therapy; Cattle Diseases - epidemiology; Cattle Diseases - immunology; Disease Models, Animal; disease resistance; Immunity; Immunization; Infections; irradiation; Larvae; Memory interference; Nematoda; nematode larvae; Nematodes; Nodules; Onchocerca; Onchocerca ochengi; Onchocerca volvulus; Onchocerciasis; Onchocerciasis - drug therapy; Onchocerciasis - epidemiology; Onchocerciasis - immunology; Onchocerciasis - veterinary; Parasites; Parasitic diseases; Parasitism; Parasitology; Prevalence; Simulium damnosum; Vaccination; Vaccines
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0601385103

Onchocerciasis (river blindness) is a major parasitic disease of humans in sub-Saharan Africa caused by the microfilarial stage of the nematode Onchocerca volvulus. Using Onchocerca ochengi, a closely related species which infects cattle and is transmitted by the same black fly vector (Simulium damnosum sensu lato) as O. volvulus, we have conducted longitudinal studies after either natural field exposure or experimental infection to determine whether, and under what circumstances, protective immunity exists in onchocerciasis. On the basis of the adult worm burdens (nodules) observed, we determined that cattle reared in endemic areas without detectable parasites (putatively immune) were significantly less susceptible to heavy field challenge than age-matched, naive controls (P = 0.002), whereas patently infected cattle, cured of infection by adulticide treatment with melarsomine, were fully susceptible. Cattle immunized with irradiated third-stage larvae were significantly protected against experimental challenge (100% reduction in median nodule load, P = 0.003), and vaccination also conferred resistance to severe and prolonged field challenge (64% reduction in median nodule load, P = 0.053; and a significant reduction in microfilarial positivity rates and density, P < 0.05). These results constitute evidence of protective immunity in a naturally evolved host-Onchocerca sp. relationship and provide proof-of-principle for immunoprophylaxis under experimental and field conditions.