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

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. 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. 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. 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.