IMMUNOTHERAPY OF CRYPTOSPORIDIOSIS USING MONOCLONALS

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Cryptosporidium parvum may produce persistent diarrheal illness in AIDS patients. The number of infected AIDS patients is likely to be underreported. Unfortunately, chemotherapeutic attempts at treatment have so far failed. Recent studies have provided evidence that treatment with hyperimmune antibody preparations may significantly reduce the severity of disease. Following through on this idea, we plan to focus on monoclonal antibody (Mab) approach to prophylaxis and treatment because these regent have uniformity, can be produced in unlimited quantity, can identify important parasite antigens and, therefore, may open up alternative treatment strategies, and can be exhaustively tested using appropriate animal model systems. Since it is likely that these Mabs will be most effective if a maximum number of life cycle stages can be neutralized, we will focus on producing neutralizing MAbs against the sporozoite merozoite and sexual stages of an Ioqa isolate of Cryptosporidium to be provided to all program projects and core facilities. the activity of these MAbs will be tested, either alone or in combination, using immunocompetent neonatal mouse models of neutralization or prophylaxis. In addition, we will test the activity of these MAbs by using an immunocompetent neonatal mouse model of treatment immunocompromised mouse models of prophylaxis and treatment, and by using improved upon or newly developed in vitro cultures to study stage-specific neutralization. Each program project will characterize and isolate relevant stage-specific antigens and will make them available for production of bovine-murine and human MAbs as an alternative treatment strategy for controlling this infection in AIDS patients. Because some of these antigens may be difficult to identify or produce, we will rely on the construction of a cDNA and genomic library and use of appropriate library expression vectors. Monoclonal antibodies showing prophylactic and treatment efficacy and which warrant clinical testing eventually will be produced in quantity.