COMPOSITIONS AND METHODS FOR ELICITING AN IMMUNE RESPONSE AGAINST CLOSTRIDIUM DIFFICILE
In one aspect, the invention relates to an immunogenic composition that includes a Clostridium difficile toxoid A and/or a C. difficile toxoid B, and methods of use thereof. In another aspect, the invention relates to a method for eliciting an immune response in a human against a C. difficile infection. The method includes administering to the human an effective dose of a composition, which includes a C. difficile toxoid, wherein the composition is administered at least two times, and wherein the immune response against C. difficile toxin A and/or toxin B is sustained.
1 . A method for eliciting an immune response in a human against Clostridium difficile expressing a toxin comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 762-840, the method comprising administering to the human a composition comprising a C. difficile toxoid and a pharmaceutically acceptable diluent.
2 . The method according to claim 15 , wherein the toxoid comprises a polypeptide comprising any one amino acid sequence selected from SEQ ID NO: 1-8, 15, 17, 19, 21, 23, 25, 28-35, 82-761, and 762-840.
3 . The method according to claim 1 , further comprising a sugar alcohol.
4 . The method according to claim 1 , further comprising sucrose.
5 . The method according to claim 1 , further comprising trehalose.
6 . The method according to claim 1 , further comprising a buffer.
7 . The method according to claim 1 , further comprising a surfactant.
8 . The method according to claim 1 , further comprising polysorbate-80.
9 . The method according to claim 1 , further comprising an adjuvant.
10 . The method according to claim 1 , further comprising aluminum hydroxide.
11 . The method according to claim 1 , further comprising a CpG oligonucleotide.
12 . The method according to claim 1 , further comprising aluminum hydroxide and a CpG oligonucleotide.
13 . The method according to claim 1 , further comprising QS-21.
14 . The method according to claim 1 , wherein the polypeptide is lyophilized.
15 . The method according to claim 1 , wherein the polypeptide comprises at least one chemically modified amino acid side chain.
16 . The method according to claim 1 , wherein the polypeptide comprises at least one amino acid side chain chemically modified by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide) (EDC).
17 . The method according to claim 1 , wherein the polypeptide comprises at least one amino acid side chain chemically modified by N-Hydroxysuccinimide (NHS).
18 . The method according to claim 1 , wherein the method comprises administering two doses of the composition.
19 . The method according to claim 18 , wherein the second dose is administered about 30 days after the first dose.
20 . A polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 763-800, wherein the polypeptide comprises a sequence less than 100% identical to SEQ ID NO: 762, wherein the polypeptide comprises at least one chemically modified amino acid side chain.
21 . The polypeptide according to claim 20 , wherein the polypeptide comprises at least one amino acid side chain chemically modified by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide) (EDC), and at least one amino acid side chain chemically modified by N-Hydroxysuccinimide (NHS).
22 . The polypeptide according to claim 20 , wherein the polypeptide comprises any one amino acid sequence selected from the group consisting of SEQ ID NOs: 842-870.
23 . A polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 802-840, wherein the polypeptide comprises a sequence less than 100% identical to SEQ ID NO: 801, wherein the polypeptide comprises at least one amino acid side chain chemically modified by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide) (EDC), and at least one amino acid side chain chemically modified by N-Hydroxysuccinimide (NHS), wherein the polypeptide comprises any one amino acid sequence selected from the group consisting of SEQ ID NOs: 871-887.
24 . A composition comprising a polypeptide according to any one of claims 20 - 23 ; and a pharmaceutically acceptable diluent.
25 . The composition according to claim 24 , further comprising a sugar alcohol.
26 . The composition according to claim 24 , further comprising polysorbate-80.
27 . The composition according to claim 24 , further comprising QS-21.
28 . The composition according to claim 24 , wherein the polypeptide is lyophilized.
29 . An antibody or antigen binding fragment thereof comprising the amino acid sequence set forth in SEQ ID NO: 841.