Cryptosporidium parvum causes a life-threatening diarrheal disease in persons with AIDS. The mechanisms by which the immune system limits infection in immunocompetent hosts has not been defined. However, antibodies directed toward cryptosporidial antigens have been shown to neutralize the invasive stages, sporozoites and merozoites; to reduce the intensity of infection when given prophylactically in animals; and to ameliorate or halt the signs of disease in immunocompromised patients when given in established infection. The goal of this proposal is to develop and use a model of cryptosporidiosis in an immunocompromised animal; the SIV-infected rhesus macaque, in order to investigate the mucosal and systemic immune response to cryptosporidial antigens, to identify antigens which are potential targets of protective antibody responses, and to test their cognate antibodies as immunotherapy of cryptosporidiosis in AIDS in the animal model.
Our specific aims are: 1. To validate the rhesus macaque-SIV model of Cryptosporidium infection in AIDS 2. To investigate the mucosal and systemic immune response to Cryptosporidium in immunologically intact and SIV-infected rhesus macaques 3. To test the capacity of antibodies to Cryptosporidium antigen(s), detected by immune macaques but not SIV-Cryptosporidium-infected macaques, for their ability to inhibit invasion and intracellular development in an in vitro model of intracellular development 4. To use the rhesus macaque SIV model to test specific immunotherapy of Cryptosporidium infection
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