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

doi:10.1073/pnas.0601385103

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

*Veterinary Parasitology, Liverpool School of Tropical Medicine and Faculty of Veterinary Science, University of Liverpool, Liverpool L3 5QA, United Kingdom;
^‡Division of Molecular Biology and Immunology, Liverpool School of Tropical Medicine, University of Liverpool, Liverpool L3 5QA, United Kingdom;
^§Institut de Recherche Agricole pour le Développement, Wakwa, BP 65 Ngaoundéré, Cameroon;
^¶Lindsay F. Kimball Research Institute, New York Blood Center, New York, NY 10021; and
^‖Tropical Medicine Research Station, P.O. Box 55, Kumba, Cameroon

Communicated by William C. Campbell, Drew University, Madison, NJ, February 22, 2006
↵ ^†V.L.T., S.P.G., and S.A.J. contributed equally to this work. (received for review November 21, 2005)

Abstract

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, naïve 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.

Footnotes

**To whom correspondence should be addressed at:
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, United Kingdom.
E-mail: trees{at}liverpool.ac.uk
Authors contributions: V.N.T., A.E.B., and A.J.T. designed research; V.L.T., S.P.G., S.A.J., B.L.M., C.K.N., L.M.N., A.E.B., and A.J.T. performed research; S.L. and P.A.E. contributed unique biological material; B.L.M. analyzed data; and V.L.T., S.P.G., B.L.M., S.L., A.E.B., and A.J.T. wrote the paper.
Conflict of interest statement: No conflicts declared.
Abbreviations:

Abbreviations:

L3,

third-stage larva;

Mf,

microfilaria;

PI,

putatively immune.