A method is provided for improving the
solubility of proteins, for example, bacterial toxins. In one embodiment,
solubility is improved by introducing point mutations that replace
cysteine residues capable of forming intermolecular disulfide bonds with other
amino acid residues that do not form such bonds. By abrogating the ability of the
cysteine residues to form inter-molecular disulfide bonds, aggregation of the
protein is reduced, thereby improving the
solubility of the
protein. In another embodiment, solubility of the
protein is improved by producing truncated forms of the protein that express the LHN domain and a fragment of the Hc domain. Proteins made according to the method of the invention are useful, for example, as immunodiagnostic agents and vaccine components.