Systemically Administered IgG Anti-Toxin Antibodies Protect the Colonic Mucosa during Infection with Clostridium difficile in the Piglet Model

Abstract

The use of anti-toxin human monoclonal antibodies (HMab) as treatment for C. difficile infection has been investigated in animal models and human clinical trials as an alternative to or in combination with traditional antibiotic therapy. While HMab therapy appears to be a promising option, how systemically administered IgG antibodies protect the colonic mucosa during Clostridium difficile infection is unknown. Using the gnotobiotic piglet model of Clostridium difficile infection, we administered a mixture of anti-TcdA and anti-TcdB HMabs systemically to piglets infected with either pathogenic or non-pathogenic C. difficile strains. The HMabs were present throughout the small and large intestinal tissue of both groups, but significant HMabs were present in the lumen of the large intestines only in the pathogenic strain-infected group. Similarly, HMabs measured in the large intestine over a period of 2–4 days following antibody administration were not significantly different over time in the gut mucosa among the groups, but concentrations in the lumen of the large intestine were again consistently higher in the pathogenic strain-infected group. These results indicate that systemically administered HMab IgG reaches the gut mucosa during the course of CDI, protecting the host against systemic intoxication, and that leakage through the damaged colon likely protects the mucosa from further damage, allowing initiation of repair and recovery.