Clostridium difficile infection (CDI) is a major cause of hospital-acquired infectious disease which brings a large healthcare burden. C. difficile is a Gram-positive, anaerobic spore-forming bacterium that is highly resistant to common disinfectants. Development of a vaccine against the pathogen is an effective and cost efficient strategy to prevent the disease caused by C. difficile. Since induction of an intestinal mucosal immune response is critical for prevention of infection, we are developing an oral vaccine by using virus-like particle incorporating C. difficile antigens. The vaccine will be administered orally to induce both systemic and gut mucosal immune responses. Success in our experiments will provide access to a vaccine that effectively prevents C. difficile infection and spread of disease.