Patent ID: 7872114

Claim:
A DNA molecule encoding an immunogenic detoxified protein which comprises the amino acid sequence of subunit A of a cholera toxin (CT-A) or the amino acid sequence of subunit A of an Escherichia coli heat labile toxin (LT-A) wherein the amino acid at the position corresponding to Ser-63 of the mature wild-type sequence is replaced with lysine and the amino acid at the position corresponding to Arg-192 of the mature wild-type sequence is replaced with glycine, and further wherein (i) the immunogenic detoxified protein is more resistant to trypsin proteolysis than wild type CT-A or LT-A; (ii) the immunogenic detoxified protein exhibits reduced toxicity as compared to a CT or LT subunit A protein in which only the amino acid residue Arg-192 is replaced with glycine; and (iii) the immunogenic detoxified protein exhibits enhanced immunogenicity as compared to a CT or LT subunit A protein in which the amino acid residue Ser-63 is replaced with lysine.