Clostridium difficile is a gram-positive, spore forming bacteria that is the most common cause of healthcare-acquired infections (HAI). C. difficile infections (CDI) results in 14,000 deaths per year in the United States mainly in older adults who take antibiotics and have prolonged hospital stays. C. difficile, which can be part of the normal microflora of the gut, usually only, causes disease when other competing bacteria of the gut are reduced by antibiotic treatment. C. difficile is spread through the fecal-oral route and its ability to form heat and acid resistant spores contributes to its ability to spread in hospitals and nursing homes. There is no current commercial vaccine for CDI and most vaccine efforts have focused on the two main virulence factors, toxin A (TcdA) and B (TcdB). Neither of these toxins alone provides complete protection against CDI, so a multivalent vaccine approach will likely be required. Another potential vaccine candidate against C. difficile is the polysaccharide capsule(s). Matrivax is currently exploring using PCMV technology to make a multivalent vaccine incorporating polysaccharide and protein antigens from C. difficile.