Immunogenic compositions comprising
The present invention relates to compositions and fusion proteins containing at least two Mycobacterium sp. antigens, and polynucleotides encoding such compositions and fusion proteins. The invention also relates to methods for their use in the treatment, prevention and/or diagnosis of tuberculosis infections.
1. A composition comprising an immunostimulant and a fusion polypeptide, wherein the fusion polypeptide comprises Mycobacterium tuberculosis antigens comprising the amino acid sequence set forth in SEQ ID NO: 41 and comprising the amino acid sequence set forth in SEQ ID NO: 46, or comprises an antigen having a sequence with at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 41 and an antigen having a sequence with at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 46.
2. The composition of claim 1 , wherein the fusion polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 236; or a sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 236.
3. The composition of claim 2 , wherein the fusion polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 236.
4. The composition of claim 3 , wherein the immunostimulant is selected from the group consisting of glucopyranosyl lipid adjuvant (GLA), AS-2, monophosphoryl lipid A, 3-de-O-acylated monophosphoryl lipid A, IFA, QS21, CWS, TDM, AGPs, CpG-containing oligonucleotides, Toll-like receptor agonists, LeIF, saponins, saponin mimetics, biological and synthetic lipid A, imiquimod, gardiquimod, resiquimod, polyI:C, flagellin, and a combination thereof.
5. The composition of claim 1 wherein the immunostimulant is selected from the group consisting of glucopyranosyl lipid adjuvant (GLA), adjuvant system-2 (AS-2), monophosphoryl lipid A, 3-de-O-acylated monophosphoryl lipid A, incomplete Freund's adjuvant (IFA), Quillaja saponaria 21 (QS21), cell wall skeleton (CWS), trehalose dicorynomycolate (TDM), aminoalkyl glucosaminide phosphates (AGPs), CpG-containing oligonucleotides, Toll-like receptor agonists, LeIF, saponins, saponin mimetics, biological and synthetic lipid A, imiquimod, gardiquimod, resiquimod, polyI:C, flagellin, and a combination thereof.
6. The composition of claim 1 , wherein the fusion polypeptide comprises Mycobacterium tuberculosis antigens comprising the amino acid sequence set forth in SEQ ID NO: 41 and comprising the amino acid sequence set forth in SEQ ID NO: 46.
7. The composition of claim 6 , wherein the fusion polypeptide further comprises a Mycobacterium tuberculosis antigen comprising the amino acid sequence set forth in SEQ ID NO: 145.
8. The composition of claim 6 , wherein the fusion polypeptide further comprises a Mycobacterium tuberculosis antigen comprising the amino acid sequence set forth in SEQ ID NO: 21.
9. The composition of claim 6 , wherein the fusion polypeptide further comprises a Mycobacterium tuberculosis antigen comprising the amino acid sequence set forth in SEQ ID NO: 163.
10. The composition of claim 1 , wherein the fusion polypeptide further comprises a Mycobacterium tuberculosis antigen comprising the amino acid sequence set forth in SEQ ID NO: 145, or an antigen having a sequence with at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 145.
11. The composition of claim 10 , wherein the fusion polypeptide further comprises a Mycobacterium tuberculosis antigen comprising the amino acid sequence set forth in SEQ ID NO: 21, or an antigen having a sequence with at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 21.
12. The composition of claim 10 , wherein the fusion polypeptide further comprises a Mycobacterium tuberculosis antigen comprising the amino acid sequence set forth in SEQ ID NO: 163, or an antigen having a sequence with at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 163.
13. The composition of claim 1 , wherein the fusion polypeptide comprises Mycobacterium tuberculosis antigens comprising the amino acid sequence set forth in SEQ ID NO: 41, comprising the amino acid sequence set forth in SEQ ID NO: 46, comprising the amino acid sequence set forth in SEQ ID NO: 145, and comprising the amino acid sequence set forth in SEQ ID NO: 21.
14. The composition of claim 1 , wherein the fusion polypeptide comprises Mycobacterium tuberculosis antigens comprising the amino acid sequence set forth in SEQ ID NO: 41, comprising the amino acid sequence set forth in SEQ ID NO: 46, comprising the amino acid sequence set forth in SEQ ID NO: 145, and comprising the amino acid sequence set forth in SEQ ID NO: 163.
15. The composition of claim 1 , wherein the antigens are directly linked.
16. The composition of claim 1 , wherein the antigens are linked via an amino acid linker.
17. The composition of claim 1 , wherein the fusion polypeptide further comprises a Mycobacterium tuberculosis antigen comprising the amino acid sequence set forth in SEQ ID NO: 21, or an antigen having a sequence with at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 21.
18. The composition of claim 1 , wherein the fusion polypeptide further comprises a Mycobacterium tuberculosis antigen comprising the amino acid sequence set forth in SEQ ID NO: 163, or an antigen having a sequence with at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 163.
19. An isolated fusion polypeptide comprising Mycobacterium tuberculosis antigens comprising the amino acid sequence set forth in SEQ ID NO: 41 and comprising the amino acid sequence set forth in SEQ ID NO: 46, or comprising an antigen having a sequence with at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 41 and an antigen having a sequence with at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 46.
20. The isolated fusion polypeptide of claim 19 , wherein the fusion polypeptide further comprises a Mycobacterium tuberculosis antigen comprising the amino acid sequence set forth in SEQ ID NO: 145, or an antigen having a sequence with at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 145.
21. The isolated fusion polypeptide of claim 20 , wherein the fusion polypeptide further comprises a Mycobacterium tuberculosis antigen comprising the amino acid sequence set forth in SEQ ID NO: 21 or comprising the amino acid sequence set forth in SEQ ID NO: 163; or an antigen having a sequence with at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 21 or an antigen having a sequence with at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 163.
22. The isolated fusion polypeptide of claim 19 , wherein the antigens are directly linked.
23. The isolated fusion polypeptide of claim 19 , wherein the antigens are linked via an amino acid linker.
24. The isolated fusion polypeptide of claim 19 , wherein the fusion polypeptide comprises the amino acid sequence set forth in SEQ ID NO:236 or a sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 236.
25. The isolated fusion polypeptide of claim 19 , wherein the fusion polypeptide comprises Mycobacterium tuberculosis antigens comprising the amino acid sequence set forth in SEQ ID NO: 41 and comprising the amino acid sequence ser forth in SEQ ID NO: 46.
26. The isolated fusion polypeptide of claim 25 , wherein the fusion polypeptide further comprises a Mycobacterium tuberculosis antigen comprising the amino acid sequence set forth in SEQ ID NO: 145.
27. The isolated fusion polypeptide of claim 25 , wherein the fusion polypeptide further comprises a Mycobacterium tuberculosis antigen comprising the amino acid sequence set forth in SEQ ID NO: 21 or the amino acid sequence set forth in SEQ ID NO:163.