Cryptosporidium: Molecular Basis of Host-Parasite Interaction

Characterization and Formulation of Multiple Epitope-Specific Neutralizing Monoclonal Antibodies for Passive Immunization against Cryptosporidiosis

“…Additional studies will be required to further define the relationship between the antigens comprising GP25-200 and CSL. Recognition of carbohydrate-dependent epitopes by many ␣GP25-200 MAbs was not unexpected, based on the glycosylated state reported for C. parvum sporozoite apical and surface proteins (20,35,48,49) and observations that glycoconjugates are important targets of the humoral immune response against C. parvum (17,19,34,35,37,38,39,49,57). Recognition of peptide epitopes by all 14 Western blot-reactive ␣P23 MAbs is consistent with the reported presence of a single N-glycosylation site in P23 (31).…”

“…Additional studies will be required to explain these unexpected observations. In any case, a compelling rationale for the use of MAb formulations targeting up to three distinct antigens rather than single MAbs is evident when considering the extended-course treatment regimens which are likely to be required for control of infection in immunodeficient hosts (8,27,35,36,51,52,53,57). If antigenic variation within or between C. parvum isolates occurs, targeting multiple epitopes with therapeutic MAbs may reduce the potential for selection and emergence of variant C. parvum subpopulations.…”

“…Knowledge of the specific mechanisms by which MAbs mediate neutralization would add to the presently limited information base on the immunobiology and molecular pathogenesis of cryptosporidiosis and might provide insight into novel control strategies (8,35,57). Therefore, we recently determined that MAb 3E2 neutralizes infectivity by binding to a sporozoite ligand contained in CSL, after which attachment is inhibited (19).…”

“…The role of C. parvum in diarrhearelated morbidity in AIDS patients and its economic impact on livestock production are now well recognized (13). No approved parasite-specific drugs, vaccines, or immunotherapies for C. parvum are presently available, although recent advances have been reported (4,8,15,17,30,32,35,41,50,57).…”

“…We reasoned that specific and selective targeting of distinct functional epitopes would result in an additive neutralizing effect with high specific activity. The rationale for this approach is that control of C. parvum infection will likely require targeting of multiple neutralization-sensitive epitopes on the infective zoite stages (8,35,57). An optimal formulation of neutralizing MAbs would be expected to control infection by binding to zoites within the intestinal lumen and preventing their attachment and invasion (22,28,35).…”