Atoxic Clostridium difficile toxin proteins were expressed in an endotoxin-free Bacillus system top develop a vaccine to reduce incidence and severity of C. difficile infection (CDI). Immunogens evaluated as potential vaccine candidates are mutated toxin A (encoded by TcdA) and toxin B (TcdB), and a rationally designed chimeric protein containing full-length TcdB protein except that the receptor binding domain is replaced with that of TcdA (designated as cTxAB). A small deletion (97 amino acids) in the transmembrane domain was used to reduce or eliminate toxicity.