Clostridioides difficile is the most common cause of healthcare associated infections (HAI).  C. difficile infections (CDI) result in 14,000 deaths per year in the United States mainly in older adults who take antibiotics and have prolonged hospital stays.  There is no vaccine for CDI and most vaccine efforts have focused on Toxin A (TcdA) and Toxin B (TcdB), which are primarily responsible for disease symptoms. Toxoid vaccine candidates may provide only limited protection against CDI since they target the toxin(s), but not the bacteria itself.  Thus, a multivalent vaccine that targets both the toxins and the bacterial surface may be a more effective approach to combating CDI.