The overall goal of this project is to examine the immune response in persons with onchocerciasis and test whether specific defined antigens may be involved in the pathogenesis of sclerosing keratitis. Onchocerciasis is one of the leading parasitic disease problems in humans. It is believed to be immune-mediated. However, the precise pathogenesis and the antigens that elicit a pathogenic immune response remain undefined. In particular, why some persons in an endemic area develop sclerosing keratitis and others chorioretinitis is unknown, as well as why some individuals develop skin disease. Furthermore, there are significant differences in prevalence of disease manifestations in different endemic areas that remain unexplained. Thus, our overall understanding of the disease process in onchocerciasis is inadequate. The present proposal is designed to capitalize upon the availability of the unique capabilities represented by, on the other hand, the established field and animal model research resources developed by the investigators over the past 10 years, and, on the other hand, by the capability to produce defined antigens of O. volvulus to examine at the molecular level the immune response in infected humans and animals models and its relationship to immunity and to disease.
The specific aims of this proposal are: (1) To rigorously define clinical subgroups in field-based examinations in endemic areas for O. volvulus in order to obtain reagents (serum and peripheral blood mononuclear cells) to select disease-associated antigens from a cDNA library made from O. volvulus. These reagents will be used in Projects 2 and 3; (2) To examine the cell-mediated and humoral immune response in O. volvulus-infected persons and controls, with and without ocular and skin disease, to disease-associated recombinant antigens identified in Projects 2 and 3. Additionally, responses in persons with chorioretinitis vs. early sclerosing keratitis will be compared; (3) To define the immune response to disease-associated recombinant antigens in areas with (a) endemic rain forest infection and (b) savannah infection; (4) As a corollary to Specific Aim 3 to compare recombinant epitopes that are associated with the high prevalence of sclerosing keratitis seen with savannah infection; and 5) To compare the immune response to disease- associated recombinant antigens in ivermectin treated subjects before and after therapy and to correlate with disease status, particularly status, particularly in those who show improvement.
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