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