Abstract: The invention relates to novel DNA and protein vaccines against Clostridium botulinum. The DNA vaccine includes a DNA molecule that includes a first segment encoding a fragment of a heavy chain region of a Clostridium botulinum neurotoxin, wherein the first segment is codon-enhanced to improve expression of the isolated DNA molecule in a mammalian host, and preferably a second segment that encodes a secretion signal peptide. The chimeric protein of the present invention includes the secretion signal peptide linked N-terminal of the fragment of a heavy chain region of a Clostridium botulinum neurotoxin. Use of these materials to raise antibodies, and to impart resistance against Clostridium botulinum to a mammal is also disclosed.