Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 15, 1998
Publication Date: N/A
Interpretive Summary: Cryptosporidiosis is an intestinal parasitic disease of humans and animals caused by the protozoan parasite Cryptosporidium parvum. Several large-scale outbreaks of cryptosporidiosis have occurred in the last decade due to the consumption of contaminated drinking water. The parasite persists in the environment because of its small size (less than 5 um) and its resistance to most disinfectants. There are also no drugs approved for treating acute or chronic disease. One potential therapy is the administration of colostrum that contains antibodies against the parasite to infected individuals. The preparation of this immune colostrum requires production of large numbers of cryptosporidial parasites for immunizing cows. Our approach in this study was to immunize pre-parturient cows with plasmid DNA coding for an antigen on the surface of the parasite. Immune colostrum that bound the parasite was produced and administered to mice prior to and for three days after infection with cryptosporidial parasites. Mice that received immune colostrum compared to mice that received normal colostrum showed partial protection against parasite development. This study showed that (1) injection of cows with DNA coding for a parasite antigen can elicit colostrum antibodies against the parasite and (2) this colostrum can be used to protect mice against cryptosporidiosis. This colostrum will now be tested in young calves for therapeutic intervention of cryptosporidiosis.
Preparturient cows were immunized with recombinant plasmid DNA encoding the Cryptosporidium parvum CP15/60. Serum was collected at each of three successive immunizations and first colostrum was collected after parturition; all were assayed for Cryptosporidium-specific antibodies (Ab). A serological response to C. parvum sporozoite and oocyst antigen was detected in cows immunized with pCP15/60 plasmid DNA. Colostrum from these cows, unlike colostrum from normal controls, contained Ab specific for C. parvum sporozoites and oocysts as indicated by immunofluorescence Ab (IFA) staining. Immune colostrum and control colostrum were administered to separate groups of dexamethasone (DEX)-treated adult C57BL/6NCr mice beginning 12 hr before and at 12 hr intervals for 3 days after oral C. parvum oocyst infection. Cryptosporidium development was assayed in ilea of immune- and control-colostrum-treated mice 96 hrs post-infection by semi-quantitative PCR. Mice receiving immune colostrum showed partial protection (about 50 % reduction) against intestinal C. parvum development compared to mice receiving control colostrum. This protection was evident at a challenge dose of 103 C. parvum oocysts per mouse; no differences were noted in parasite development between groups receiving immune or control colostrum and infected with 104 oocysts. This study showed that serum and colostrum Ab response to C. parvum can be elicited in preparturient cows by direct injection of recombinant pCP15/60 plasmid DNA and that passive protection against cryptosporidiosis can be obtained by treating immunosuppressed mice with immune colostrum before and after C. parvum infection.