Characterisation of Protective Antibodies in Hamsters Immunised AgainstClostridium difficileToxins A and B

Abstract
Toxigenic Clostridium difficile is the major cause of antimicrobial agent-associated pseudomembranous colitis in humans and of ileocaecitis in golden Syrian hamsters. The pathogenicity of C.difficile is believed to be dependent on the production of two immunologically and biochemically distinct toxins: toxin A (enterotoxin) and toxin B (cytotoxin). In earlier investigations we demonstrated that hamsters immunised against toxins A and B are protected against clindamycin-induced C. difficile-associated ileocaecitis and that this protection is transferred to infant hamsters through maternal milk. In the present investigation, the class-specific immunoglobulin response in adult and infant hamsters immunised against C.difficile toxins A and B was examined using enzyme linked immunosorbent assays. Parenteral immunisation of adult hamsters against toxins A and B induced IgG, IgA and IgM antibodies in hamster sera specific for these two toxins. IgG antibodies to toxins A and B predominated in the milk and intestines of adult hamsters immunised against toxins A and B and in the sera and intestine of infants from immunised adult hamsters. No significant IgA or IgM antibodies to toxins A and B were detected in maternal milk and intestines or in infant sera and intestines. IgG antibodies to toxins A and B were detected in infant caecal contents up until 10 d and in sera up until approximately 24 d of age. The results from this investigation suggest that serum derived IgG antibody to C.difficile toxins is primarily responsible for protection of adult and infant hamsters against C.difficile-associated ileocaecitis when immunised parenterally against toxins A and B.