Passive Immunisation of Hamsters against Clostridium Difficile Infection using Antibodies against Surface Layer Proteins

Aims: Clostridium difficile is the primary cause of antibiotic-associated diarrhoea and a frequent cause of pseudomembranous colitis. We assessed the ability of high specificity, high-titre rabbit anti-C. difficile surface layer protein (SLP) antibodies to protect against infection in a lethal hamster model.

Methods: Rabbit antiserum was raised against SLPs purified from a clinical isolate of C. difficile. Hamsters were infected with 10⁵ C. difficile four hours post-clindamycin administration. In the experimental group (n=8), the inoculum was incubated with immune serum, and additional doses of serum given pre- and post-infection. Control groups were treated with irrelevant serum (n=8) or untreated (n=4).

Results: All hamsters developed diarrhoea with no significant difference in time of onset. However, post-challenge survival time (hours) was significantly increased in animals treated with anti-SLP antiserum (median=156.88, range=62.5–221.5) compared with animals treated with irrelevant serum (76.625, 55.17–143) (p=0.0281) or untreated (69.625, 55.33–126.42) (p=0.0283).

Conclusions: Rabbit anti-C. difficile SLP antibodies modify the course of C. difficile infection in hamsters. This indicates that the SLPs are potentially protective antigens and are therefore candidates for a vaccine or component of a composite vaccine against C. difficile.