Research and Diagnostic Applications of Monoclonal Antibodies to 'Coccidioides immitis'

摘要

The authors have been assembling a panel of mouse monoclonal antibodies to antigens on the surface of endospores and spherules, and in culture filtrates and soluble extracts of spherule-phase C. immitis. These antibodies are being used to develop antigen-trapping EIA, latex agglutination and fluorescence immnodiagnostic tests, to conduct immunoaffinity purification of the antigens, and to prepare drug-conjugated Fab fragments as reagents for inhibiting C. immitis development. In experiments with soluble and particulate antigens from 7 other human pathogenic fungi, gel chromatography, enzyme immunoassay and immunoblot methods revealed antigenic determinants unique to C. immitis and at least one shared with Histoplasma capsulatum. The immunoreactivity of the hybridoma antibodies and sera from several infected subjects has been compared to identify monoclonal antibodies to antigens which elicit the human immune response. Experiments are under way to identify epitopes that can serve as markers for genetic variants of C. immitis, and antibodies which may be useful for screening recombinant DNA libraries for expression of C. immitis genes. The authors will outline the current status of similar efforts in other fungal systems, and present strategies which we have found useful for selecting and utilizing suitable monoclonal antibodies.