Compositions for treatment of celiac disease
The invention provides agents and vaccines for treating and diagnosing celiac disease. In particular, the present invention provides a combination of three peptides that are useful for treating and diagnosing celiac disease in a large proportion of patients.
1. An agent comprising:
i) a first peptide comprising SEQ ID NO:3 or SEQ ID NO:4
ii) a second peptide comprising SEQ ID NO:10 or SEQ ID NO:15, and
iii) a third peptide comprising SEQ ID NO:17 or SEQ ID NO:18 or SEQ ID NO:19.
2. The agent of claim 1 , wherein the second peptide comprises SEQ ID NO:320, and/or the third peptide comprises SEQ ID NO:321.
3. The agent of claim 1 , wherein the first, second and/or third peptide comprises an N-terminal acetyl group or pyroglutamate group, and/or a C-terminal amide group.
4. The agent of claim 3 , wherein the first, second and/or third peptide comprises an N-terminal pyroglutamate group and a C-terminal amide group.
5. The agent of claim 1 , wherein the first, second and/or third peptide is conjugated to a compound.
6. The agent of claim 5 , wherein the compound is an adjuvant, or a major histocompatibility (MHC) molecule or binding fragment thereof.
7. The agent of claim 1 , wherein two or three of the first, second and third peptides are on a single polypeptide chain.
8. The agent of claim 1 comprising one or more additional peptides comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:47, 48, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 75, 76, 77, 78, 79, 80, 81, 89, 90, 91, 92, 95, 102, 103, 104, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 136, 169, 170, 171, 172, 173, 174, 177, 178, 179, 180, 183, 184, 187, 188, 189, 190, 191, 192, 209, and 210.
9. The agent of claim 1 , comprising:
i) a first peptide comprising SEQ ID NO:3 and SEQ ID NO:4,
ii) a second peptide comprising SEQ ID NO:10 and SEQ ID NO:15, and
iii) a third peptide comprising SEQ ID NO:17 and either SEQ ID NO:18 or SEQ ID NO:19.
10. The agent of claim 1 , wherein each of the first, second, and third peptides is independently between 7 to 50 amino acids in length.
11. The agent of claim 1 , wherein each of the first, second, and third peptides is 20 or fewer amino acids in length.
12. The agent of claim 10 , wherein each of the first, second, and/or third peptide is 11 amino acids in length.
13. The agent of claim 10 , wherein each of the first, second, and/or third peptide is 14 amino acids in length.
14. The agent of claim 10 , wherein each of the first, second, and/or third peptide is 15 amino acids in length.
15. The agent of claim 10 , wherein each of the first, second, and/or third peptide is 16 amino acids in length.
16. The agent of claim 10 , wherein each of the first, second, and/or third peptide is 17 amino acids in length.
17. The agent of claim 10 , wherein each of the first, second, and/or third peptide is 18 amino acids in length.
18. An agent comprising:
i) a first peptide consisting of SEQ ID NO:13 and an N-terminal and/or C-terminal modification,
ii) a second peptide consisting of SEQ ID NO:14 and an N-terminal and/or C-terminal modification, and
iii) a third peptide consisting of SEQ ID NO:16 and an N-terminal and/or C-terminal modification.
19. An agent comprising:
i) a first peptide consisting of SEQ ID NO:228,
ii) a second peptide consisting of SEQ ID NO:229, and
iii) a third peptide consisting of SEQ ID NO:230.
20. A vaccine comprising the agent of claim 1 , and a pharmaceutically acceptable carrier.
21. A kit comprising the agent of claim 1 , and means to detect binding of one or more peptides to T cells.