A DNA vaccine targeting TcdA and TcdB induces protective immunity against Clostridium difficile

BACKGROUND: Clostridium difficile-associated disease (CDAD) constitutes a great majority of hospital diarrhea cases in industrialized countries and is induced by two types of large toxin molecules: toxin A (TcdA) and toxin B (TcdB). Development of immunotherapeutic approaches, either active or passive, has seen a resurgence in recent years. Studies have described vaccine plasmids that express either TcdA and/or TcdB receptor binding domain (RBD). However, the effectiveness of one vector encoding both toxin RBDs against CDAD has not been evaluated. METHODS: In the study, we constructed highly optimized plasmids to express the receptor binding domains of both TcdA and TcdB from a single vector. The DNA vaccine was evaluated in two animal models for its immunogenicity and protective effects. RESULTS: The DNA vaccine induced high levels of serum antibodies to toxin A and/or B and demonstrated neutralizing activity in both in vitro and in vivo systems. In a C. difficile hamster infection model, immunization with the DNA vaccine reduced infection severity and conferred significant protection against a lethal C. difficile strain. CONCLUSIONS: This study has demonstrated a single plasmid encoding the RBD domains of C. difficile TcdA and TcdB as a DNA vaccine that could provide protection from C. difficile disease.