Immunology

Biography

Biography: Xingmin Sun

Abstract

Clostridium difficile is the major cause of hospital-acquired infectious diarrhea and colitis in developed countries. The pathogenicity of C. difficile is mainly mediated by the release of two potent large exotoxins, toxin A (TcdA) and toxin B (TcdB), both of which are pathogenic and require neutralization to prevent disease occurrence. We have constructed a novel recombinant fusion protein, designated mTcd138, containing the receptor binding domain of TcdA and the glucosyltransferase and cysteine proteinase domains of TcdB and expressed it in Bacillus megaterium. To ensure mTcd138 is atoxic, two point mutations were made in the glucosyltransferase domain of TcdB, which essentially eliminates the toxicity. Parenteral immunizations of mice with mTcd138 induced highly protective antibodies to both toxins and provided full protection against parenteral toxin challenges with lethal doses of toxins and infection with a hyper-virulent C. difficile strain UK6. Our studies demonstrate the potential of mTcd138 as a vaccine candidate against CDI in humans.