Isolated polypeptide of the toxin A and toxin B proteins of
This present invention provides C-TAB.G5 and C-TAB.G5.1 isolated polypeptides comprising the receptor binding domains of C. difficile toxin A and toxin B as set forth in the amino acid sequences of SEQ ID NO: 2 and SEQ ID NO: 4. The C-TAB.G5 and C-TAB.G5.1 isolated polypeptides may be used to neutralize toxic effects of C. difficile toxin A and/or toxin B.
1. An isolated polypeptide comprising
a first C-terminal portion from Clostridium difficile ( C. difficile ) toxin A and
a second C-terminal portion from C. difficile toxin B,
wherein the second C-terminal portion from C. difficile toxin B comprises amino acids 1988-2366 corresponding to SEQ ID NO: 8 and does not comprise amino acids 1834-1967 corresponding to SEQ ID NO: 8.
2. The isolated polypeptide of claim 1 , wherein the first C-terminal portion from C. difficile toxin A comprises amino acids 2121-2686 corresponding to SEQ ID NO: 6.
3. The isolated polypeptide of claim 1 , wherein the first C-terminal portion from C. difficile toxin A comprises amino acids 2276-2710 corresponding to SEQ ID NO: 6.
4. The isolated polypeptide of claim 1 , wherein the first C-terminal portion from C. difficile toxin A comprises amino acids 2276-2686 corresponding to SEQ ID NO: 6.
5. The isolated polypeptide of claim 1 , wherein the first C-terminal portion from C. difficile toxin A does not comprise amino acids 2687-2710 corresponding to SEQ ID NO: 6.
6. The isolated polypeptide of claim 1 , wherein the polypeptide comprises at least 19 repeating units derived from the C-terminal domain of C. difficile toxin A.
7. The isolated polypeptide of claim 1 , wherein the polypeptide comprises fewer than 23 repeating units derived from the C-terminal domain of C. difficile toxin B.
8. The isolated polypeptide of claim 1 , wherein the polypeptide is capable of inducing neutralizing antibodies against both C. difficile toxins A and B.
9. A pharmaceutical composition comprising the isolated polypeptide of claim 1 and a pharmaceutically acceptable carrier or excipient.
10. The pharmaceutical composition of claim 9 , further comprising a therapeutic agent selected from the group consisting of anesthetics, analgesics, anti-inflammatories, steroids, antibiotics, antiarthritics, anorectics, antihistamines and antineoplastics.
11. The pharmaceutical composition of claim 9 , further comprising an adjuvant.
12. The pharmaceutical composition of claim 11 , wherein the adjuvant comprises alum.