Effects of immune colostrum and orally administered antisporozoite monoclonal antibodies on the outcome of Cryptosporidium parvum infections in neonatal mice

Abstract

A neonatal BALB/c mouse model of cryptosporidiosis was used to examine the potential passive transfer of immunity via immune colostrum and oral treatment with anticryptosporidial monoclonal antibodies. Neonates suckled by dams that recovered from Cryptosporidium parvum infections were equally susceptible to infection as their control counterparts suckled by naive dams. Parasite loads among the control and immune colostrum-fed mice were indistinguishable. Neonates receiving orally administered antisporozoite monoclonal antibodies were equally susceptible to infections compared with the control and immune colostrum-fed mice. Parasite loads among the mice receiving daily oral treatment with monoclonal antibody mixtures exhibited significantly lower parasite loads compared with the control mice (P < 0.05). Cryptosporidium parvum is a protozoan (coccidian) parasite that infects the intestinal epithelium of a variety of mammals. Infection is often accompanied by symptoms of gastroenteritis and diarrhea (6). In immunocompetent hosts the disease is self-limiting, and resolution is accompanied by antibody production to various life-cycle stages (2, 3, 15, 26, 28, 29). Immunodeficient humans (those with acquired immune deficiency syndrome and hypogammaglobulinemia) and mice (athymic) may exhibit persistent infections (6, 8, 10, 16, 18). Humoral and cell-mediated immune responses are apparently necessary for recovery from cryptosporidiosis.

Virus-Neutralizing Monoclonal Antibody Expressed in Milk of Transgenic Mice Provides Full Protection against Virus-Induced Encephalitis

“…In some instances (e.g., if vaccination is ineffective or if infection with live pathogens results in high mortality), alternative routes have to be employed to provide passive immunization to mammalian offspring. Purified neutralizing MAbs can be injected into pregnant or lactating host animals (5) or directly administered to neonates (2,38). In order to generate milk which contains antibodies of therapeutic value, animals which are not the natural host (preferably ruminants, which yield large amounts of milk) can be immunized with live pathogens (7,17).…”

Role of Immunoglobulin A Monoclonal Antibodies against P23 in Controlling MurineCryptosporidium parvumInfection

“…Ags deposited in trails may be important functional target Ags because they are deposited during locomotion and are shed during invasion of host cells (3,16,38). Spleen-derived MAbs against GP15 (monomeric IgA) and P23 (IgG1) have been shown to decrease infection levels in mouse models, indicating that GP15 and P23 contain neutralization-sensitive epitopes (1,26,31,37). Because P23 is conserved among geographically diverse bovine and human C. parvum isolates (26), present in both infectious zoite stages, deposited during zoite motility, and known to contain neutralization-sensitive epitopes, it may be a biologically relevant Ag which can be targeted for immunological intervention.…”

“…The utility of Abs in the control of intestinal cryptosporidiosis is exemplified by passive immunotherapy studies with polyclonal Abs and MAbs (reviewed in reference 31). Anti-C. parvum MAbs, and polyclonal Abs in hyperimmune hen egg yolk and secretory IgG1-rich hyperimmune bovine colostrum, have been efficacious in the control of intestinal cryptosporidiosis in immunologically immature or immunocompromised rodent models (1,5,9,12,25,26,32,34,37). Hyperimmune polyclonal Ab preparations have had variable efficacy against intestinal C. parvum infection in immunocompromised humans (24,39,40,42).…”

“…Because IgA conferred protection against these mucosal pathogens and Ag-specific IgA responses occur in hosts with cryptosporidiosis, we hypothesized that IgA directed to neutralization-sensitive epitopes may be useful in passive immunization against C. parvum. To determine whether IgA can influence the course of C. parvum infection, we produced dimeric IgA MAbs to P23, a previously defined C. parvum Ag containing neutralization-sensitive epitopes (1,3,21,26). Here we report that dimeric anti-P23 IgA MAbs have efficacy against intestinal C. parvum infection in neonatal mice.…”

“…No commercially available antiparasite chemotherapy is consistently effective in treating such patients (6). Passive immunization with antibodies (Abs) against whole C. parvum organisms has variable efficacy in immunocompromised or neonatal hosts (1,5,9,12,24,25,31,37,39,40,42). Recovery from and resistance to cryptosporidiosis require principally cellular, but also humoral, immune components in immunocompetent hosts (31,45).…”