Cryptosporidium is a sporozoan parasite which replicates in the surface epithelium of the gastrointestinal and/or respiratory tract of man and other animals. Infection of immunocompetent patients results in self-limiting gastrointestinal influenza-like symptoms, but severe longstanding and life-threatening diarrhea is observed in immunodeficient patients, including those with the acquired immunodeficiency syndrome (AIDS). The severity of disease in AIDS patients is explained by two factors: 1) inability to terminate infection because of suppressed immune responsiveness and absence of effective chemotherapeutic agents, and 2) the autoinfective nature of the life cycle of Cryptosporidium, allowing merozoites and sporozoites to infect additional cells and perpetuate disease even though the patients is not re-exposed to an exogenous source of the organism. These problems could be circumvented and the disease controlled if patients received antibodies with neutralizing activity for merozoites and sporozoites of Cryptosporidium. Our research will test the hypothesis that cryptosporidiosis can be prevented and treated by administration of neutralizing antibodies reactive with infective stages of the organism. This will be accomplished by pursuing the following specific aims. 1: Produce neutralizing antibodies reactive with surface antigens of Cryptosporidium sporozoites. 2: Test sporozoite neutralizing antibodies for ability to protect against challenge by Cryptosporidium oocysts. 3: Produce neutralizing antibodies reactive with surface antigens of Cryptosporidium merozoites. 4: Test neutralizing antibodies, reactive with sporozoites and merozoites, for ability to terminate existing Cryptosporidium infection.
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