Passive immunization of hamsters against disease caused by Clostridium difficile by use of bovine immunoglobulin G concentrate

Abstract

Gestating Holstein cows were vaccinated with Clostridium difficile toxoid prepared from the culture filtrate of a strain that produces high levels of toxins A and B and other antigens. A bovine immunoglobulin G (IgG) concentrate was prepared from colostrum collected at parturition. The results of our studies showed that hamsters treated prophylactically with the hyperimmune bovine IgG concentrate were protected against C. difficile disease. These results suggest that orally administered hyperimmune bovine IgG specific for C. difficile culture ifitrate may be useful in prophylaxis against C. difficile disease.

Clostridium difficile: Recent Epidemiologic Findings and Advances in Therapy

“…Anti-C. difficile bovine immunoglobulin neutralizes the effects of toxin B in the cell cytotoxicity assay and has been used to treat and prevent CDAD in rodents. 1,86 Use of monoclonal antibody to toxin A has shown promising results in animals, and phase II studies in humans are in progress 87 using CDA1 and MDX-1388, human monoclonal antibodies to toxin A and toxin B. Surgical intervention is reserved for patients who do not respond to medical treatment or when colonic perforation or toxic megacolon is suspected. 88,89…”

Physical Characterization of Clostridium Difficile Toxins and Toxoids: Effect of the Formaldehyde Crosslinking on Thermal Stability

“…15 Thus, vaccination using toxoids A and B appears as a promising approach to prevent CDAD and to control reccurences. [10][11][12][13][14][15] C. difficile toxins A and B exhibit 49% amino acid identity and belong to the large clostrodial cytotoxin (LCT) family, which includes the Clostridium sordelii toxins and Clostridium novyi alpha toxin. Toxins A and B possess high molecular weight, an amino-terminal enzymatic domain (e.g., residues 1-543), a central hydrophobic region (e.g., residues 900-1200) and a carboxy-terminal domain carrying carbohydrate recognition sequence repeats (e.g., residues 1750-2710 or 2366).…”

“…In hamsters, parenteral administration of formaldehyde crosslinked (inactivated) toxoids A and B can prevent lethal intestinal inflammation induced by C. difficile. [10][11][12][13] In humans, intramuscular administration of toxoids A and B was highly immunogenic and well tolerated. 14 In addition, vaccination of three patients with relapsing CDAD was associated with resolution of symptoms.…”

Passive Immunization

“…difficile-associated disease pathogenesis. Oral administration of chicken IgY and bovine antibody directed against toxin A and B was protective in the hamster model of infection (Kelly et al, 1996;Kink and Williams, 1998;Lyerly et al, 1991;Roberts et al, 2012). Targeting other Cl.…”