Human infection with the filarial parasite Onchocerca volvulus, onchocerciasis, or river blindness, is a chronic disease which affects an estimated 20 million humans throughout Africa, Mexico, Central and South America. Onchocerciasis is the second leading cause of infectious blindness in the world, and there is no medication which can cure or prevent this disease. An accepted theory regarding the pathogenesis of onchocerciasis states that disease is initiated by exposure to specific parasite protein epitopes, but that the spectrum of clinical disease manifestations reflects a modulation of the host immune response. The response is a result of both genetic and environmental factors. The objectives of this proposal will investigate this theory of disease production in Ecuadorians with onchocerciasis. Naturally occurring antibodies to 0. volvulus antigen in persons with onchocerciasis have been used to identify specific proteins which may be important in serological or cell mediated immune responses to African onchocerciasis. Research in onchocerciasis has demonstrated that well-defined, purified or recombinant proteins derived from 0. volvulus are preferable to crude antigen preparations for precise immunological investigations. Recent epidemiological studies offer compelling evidence that Ecuador is an ideal site to study onchocerciasis. In particular, local transmission of disease to both Amerindians and blacks of African origin results in different clinical manifestations in each race, and the intensity of disease transmission results in a large number of children with congenital onchocerciasis. In phase 1, experiments are designed to clearly define antibody responses to 0. volvulus antigens by Western blot analysis. Antifilarial antibodies produced by humans with onchocerciasis will be used in immunological screening strategies to identify recombinant 0. volvulus proteins which may be important in modulation of the human immune response. Phase 11 objectives will be to fully characterize recombinant 0. volvulus proteins isolated from existing and new cDNA expression libraries, and to investigate the effect of chronic exposure to parasite antigen on expression of cell surface markers. Recombinant proteins identified in this work will have a number of possible uses: in diagnostic assays, new vaccines or to demonstrate mechanisms by which parasite antigens modulate the host response to onchocerciasis.
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