The long-range objectives of this project are to characterize the clinical and immunologic features of experimentally induced Cryptosporidium infection in the pigtailed macaque and to identify and define the immunologically significant surface antigens of the sporozoite stage and of the oocyst. Over the past three years, Cryptosporidium infection has been recognized as a common cause of severe diarrhea in patients with AIDS and as a significant contributant to diarrheal disease in preschool children. Research into the components of the host immune response in cryptosporidiosis has been hampered by the lack of a suitable animal model for human cryptosporidiosis. Infant macaques develop an enteritis following natural or experimental infection with Cryptosporidium which bears strong clinical resemblance to cryptosporidiosis in young children. Given the similarities between the human and primate immune systems, investigations into the natural history of the infection, time course for development of specific humoral immunity as measured by ELISA for sporozoite or oocyst specific IgG, IgM and IgA, and the clinical and immunologic response to rechallenge in this primate model may help to elucidate the corresponding aspects of the human disease. Rapid progress towards the characterization of a retrovirus-induced simian """"""""AIDS"""""""" model at the Primate Center offers the opportunity to study experimentally induced cryptosporidiosis in an animal model with many immunologic similarities to human AIDS. Once the parameters (inoculum, incubation period, natural history) of these experimentally induced infections have been defined, the effects of modulation of the host immune system, or of specific passive immunotherapy, can be assessed. Results from these studies may have applicability to the therapy or prevention of cryptosporidiosis in humans, particularly in AIDS patients. Immunochemical analysis of the significant surface antigens will complement the above studies. Oocyst and sporozoite forms will be purified and analyzed by polyacrylamide gel electrophoresis and nitrocellulose immuno-blotting. Lactoperoxidase labeling techniques will be used to determine surface localization. Identification of specific antigens which are important in the protective host immune response may provide a basis for development of active immunotherapies.
| Miller, R A; Bronsdon, M A; Morton, W R (1991) Failure of breast-feeding to prevent Cryptosporidium infection in a primate model. J Infect Dis 164:826-7 |
| Miller, R A; Bronsdon, M A; Kuller, L et al. (1990) Clinical and parasitologic aspects of cryptosporidiosis in nonhuman primates. Lab Anim Sci 40:42-6 |
| Miller, R A; Bronsdon, M A; Morton, W R (1990) Experimental cryptosporidiosis in a primate model. J Infect Dis 161:312-5 |
