Modified tuberculosis antigens
Modified Rv3616c proteins and their use as medicaments, particularly for the prevention of reactivation of tuberculosis.
1. A modified mycobacterium Rv3616c protein comprising a first polypeptide and a second polypeptide, the first polypeptide being located towards the N-terminus relative to the second polypeptide, and wherein:
(i) the first polypeptide having at least 98% identity to residues 1-134 of SEQ ID No: 1; and
(ii) the second polypeptide having at least 98% identity to residues 155-392 of SEQ ID No: 1;
wherein the first and second polypeptides are directly linked or indirectly linked via a third polypeptide,
wherein said third polypeptide has at least 80% identity to a sequence corresponding to residues 135-154 in SEQ ID No:1 in which a contiguous portion of at least 3 amino acids has been deleted.
2. A pharmaceutical composition comprising:
(a) a modified Rv3616c protein according to claim 1 ; and
(b) a pharmaceutically acceptable carrier or excipient.
3. An immunogenic composition comprising:
(a) a modified Rv3616c protein according to claim 1 ; and
(b) a non-specific immune response enhancer.
4. A fusion protein comprising a modified Rv3616c protein according to claim 1 and an additional heterologous polypeptide.
5. The modified Rv3616c protein according to claim 1 , wherein the third polypeptide is a sequence having at least 95% identity to a sequence corresponding to residues 135-154 in SEQ ID No:1 in which a contiguous portion of at least 3 amino acids has been deleted.
6. The modified Rv3616c protein according to claim 1 , wherein the second polypeptide has at least 99% identity to residues 155-392 of SEQ ID No: 1.
7. The modified Rv3616c protein according to claim 6 , wherein the third polypeptide is a sequence having at least 95% identity to a sequence corresponding to residues 135-154 in SEQ ID No:1 in which a contiguous portion of at least 3 amino acids has been deleted.
8. A modified mycobacterium Rv3616c protein comprising the amino acid sequence of any one of SEQ ID Nos: 163, 165, 166, 167, 168, 169, 179 and 180.
9. The modified mycobacterium Rv3616c protein according to claim 8 , consisting of the amino acid sequence consisting of any one of SEQ ID Nos: 163, 165, 166, 167, 168, 169, 179 or 180.
10. The modified Rv3616c protein according to claim 8 , comprising the amino acid sequence of SEQ ID No: 163.
11. The modified Rv3616c protein according to claim 8 , comprising the amino acid sequence of SEQ ID No: 165.
12. The modified Rv3616c protein according to claim 8 , comprising the amino acid sequence of SEQ ID No: 166.
13. The modified Rv3616c protein according to claim 8 , comprising the amino acid sequence of SEQ ID No: 167.
14. The modified Rv3616c protein according to claim 8 , comprising the amino acid sequence of SEQ ID No: 168.
15. The modified Rv3616c protein according to claim 8 , comprising the amino acid sequence of SEQ ID No: 169.
16. The modified Rv3616c protein according to claim 8 , comprising the amino acid sequence of SEQ ID No: 179.
17. The modified Rv3616c protein according to claim 8 , comprising the amino acid sequence of SEQ ID No: 180.
18. The modified Rv3616c protein according to claim 9 , consisting of the amino acid sequence of SEQ ID No: 163.
19. The modified Rv3616c protein according to claim 9 , consisting of the amino acid sequence of SEQ ID No: 165.
20. The modified Rv3616c protein according to claim 9 , consisting of the amino acid sequence of SEQ ID No: 166.
21. The modified Rv3616c protein according to claim 9 , consisting of the amino acid sequence of SEQ ID No: 167.
22. The modified Rv3616c protein according to claim 9 , consisting of the amino acid sequence of SEQ ID No: 168.
23. The modified Rv3616c protein according to claim 9 , consisting of the amino acid sequence of SEQ ID No: 169.
24. The modified Rv3616c protein according to claim 9 , consisting of the amino acid sequence of SEQ ID No: 179.
25. The modified Rv3616c protein according to claim 9 , consisting the of amino acid sequence of SEQ ID No: 180.