ROLE OF IMMUNOGLOBULIN-A MONOCLONAL-ANTIBODIES AGAINST P23 IN CONTROLLING MURINE CRYPTOSPORIDIUM-PARVUM INFECTION

Cryptosporidium parvum is an important diarrhea-causing protozoan para site of immunocompetent and immunocompromised hosts. Immunoglobulin A (IgA) has been implicated in resistance to mucosal infections,vith bac teria, viruses, and parasites, but little is known about the role of I gA in the control of C. parvum infection. We assessed the role of IgA during C, parvum infection in neonatal mice. IgA-secreting hybridomas were developed by using Peyer's patch lymphocytes From BALB/c mice whi ch had been orally inoculated with viable C, parvum oocysts. Six monoc lonal antibodies (MAbs) were Selected for further study based on indir ect immunofluorescence assay reactivity with sporozoite and merozoite pellicles and the antigen (Ag) deposited on glass substrate by gliding sporozoites, Each MAb was secreted in dimeric form and recognized a 2 3-kDa sporozoite Ag in Western immunoblots. The Ag recognized comigrat ed in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with P 23, a previously defined neutralization-sensitive zoite pellicle Ag, M Abs were evaluated for prophylactic or therapeutic efficacy against C. parvum, singly and in combinations, in neonatal BALB/c mice. A combin ation of two MAbs given prophylactically prior to and 12 h following o ocyst challenge reduced the number of intestinal parasites scored hist ologically by 21.1% compared to the numbers in mice given an isotype-m atched control MAb (P < 0.01), Individual MAbs given therapeutically i n nine doses over a 96-h period following oocyst challenge increased e fficacy against C, parvum infection, Four MAbs given therapeutically e ach reduced intestinal infection 34.4 to 42.2% compared to isotype-mat ched control MAb-treated mice (P < 0.05). One MAb reduced infection 63 .3 and 72.7% in replicate experiments compared to isotype-matched cont rol MAb-treated mice (P < 0,0001). We conclude that IgA MAbs directed to neutralization-sensitive P23 epitopes may have utility in passive i mmunization against murine C., parvum infection.