Debilitating infections due to Cryptosporidium parvum in AIDS patients are likely the result of the continued unchecked recycling of type I meront and autoinfective sporont stages. The logarithmic multiplication of type I merozoites has been cited as contributing most significantly to the overwhelming infection in these patients. There are presently no effective chemotherapeutic agents available to combat this infection. Evidence has emerged, however, to suggest that stage specific or cross reactive antibodies, including monoclonals, may be useful in abrogating such infections. The main objective of this one year final continuation project, therefore, will be to complete work on identifying and characterizing individual and pooled MAbs derived from merozoites which then can be passed on to Project 2 and used in conjunction with MAbs derived against the sporozoite stage to determine the optimal pool of MAbs having neutralization efficacy against C. parvum. Specific approaches to be taken to accomplish this objective will include; 1) completing the characterization and neutralization testing of current and newly derived mAbs utilizing in vitro models of infection and 2) scaling up MAb production of select merozoite neutralization-sensitive epitopes utilizing an in vitro bioreactor system. The endpoint objective is to provide the most useful of the anti-merozoite MAbs for testing and pooling with anti-sporozoite MAbs which can be tested in both Balb/c and SCID mouse models against intestinal cryptosporidiosis. Pursuit of these objectives should help define optimal strategies for preventing or treating C. parvum infections in AIDS patients.
