Immune-based treatment and prevention of Clostridium difficile infection

Abstract

Clostridium difficile (C. difficile) causes over 500,000 infections per year in the US, with an estimated 15,000 deaths and an estimated cost of $1-3 billion. Moreover, a continual rise in the incidence of severe C. difficile infection (CDI) has been observed worldwide. Currently, standard treatment for CDI is the administration of antibiotics. While effective, these treatments do not prevent and may contribute to a disease recurrence rate of 15-35%. Prevention of recurrence is one of the most challenging aspects in the field. A better knowledge of the molecular mechanisms of the disease, the host immune response and identification of key virulence factors of C. difficilenow permits the development of immune-based therapies. Antibodies specific for C. difficile toxins have been shown to effectively treat CDI and prevent disease relapse in animal models and in humans. Vaccination has been recognized as the most cost-effective treatment/prevention for CDI. This review will summarize CDI transmission, epidemiology, major virulent factors and highlights the rational and the development of immune-based approaches against this remerging threat.

Keywords: AAD, antibiotic-associated diarrhea; CDI, Clostridium difficile infection; CPD, cysteine proteinase domain; GTD, glucosyltransferase domain; HuMabs, human monoclonal antibodies; IVIG, intravenous immunoglobulin; RBD, receptor binding domain; SLP, surface-layer protein; TMD, transmembrane domain; bacterial toxins; clostridium difficile infection (CDI); immunotherapy; mAb, monoclonal antibody; monoclonal antibody; vaccine.