Vaccines comprising
Compositions and methods for preventing, treating and detecting leprosy are disclosed. The compositions generally comprise polypeptides comprising one or more Mycobacterium leprae antigens as well as polynucleotides encoding such polypeptides.
1. A fusion polypeptide comprising Mycobacterium leprae ( M. leprae ) antigens ML2028, ML2055, and ML2380, or M. leprae antigens having at least 90% amino acid sequence identity to ML2028, ML2055, and ML2380.
2. The fusion polypeptide of claim 1 , wherein ML2028 comprises the sequence of SEQ ID NO: 2, or a sequence having at least 90% amino acid sequence identity thereto.
3. The fusion polypeptide of claim 1 , wherein ML2028 comprises the sequence of SEQ ID NO: 4, or a sequence having at least 90% amino acid sequence identity thereto.
4. The fusion polypeptide of claim 1 , wherein ML2055 comprises the sequence of SEQ ID NO: 6, or a sequence having at least 90% amino acid sequence identity thereto.
5. The fusion polypeptide of claim 1 , wherein ML2380 comprises the sequence of SEQ ID NO: 8, or a sequence having at least 90% amino acid sequence identity thereto.
6. The fusion polypeptide of claim 1 , further comprising M. leprae antigen ML2531 or an M. leprae antigen having at least 90% amino acid sequence identify to ML2531.
7. The fusion polypeptide of claim 6 , wherein the fusion polypeptide comprises the sequence of SEQ ID NO: 12, or a sequence having at least 90% amino acid sequence identity thereto.
8. The fusion polypeptide of claim 6 , wherein ML2531 comprises the sequence of SEQ ID NO: 10, or a sequence having at least 90% amino acid sequence identity thereto.
9. A composition comprising the fusion polypeptide of claim 1 .
10. The composition of claim 9 , further comprising an immunostimulant.
11. The composition of claim 10 , wherein the immunostimulant is selected from the group consisting of a CpG-containing oligonucleotide, synthetic lipid A, monophosphoryl lipid A (MPL), saponins, saponin mimetics, amino alkyl glucosaminide 4-phosphates (AGPs), Toll-like receptor agonists, or a combination thereof.
12. The composition of claim 10 , wherein the immunostimulant is selected from the group consisting of a TLR4 agonist, a TLR7/8 agonist and a TLR9 agonist.
13. The composition of claim 10 , wherein the immunostimulant is selected from the group consisting of glucopyranosyl lipid A (GLA), CpG-containing oligonucleotide, imiquimod, gardiquimod and resiquimod.
14. The composition of claim 13 , wherein the immunostimulant is GLA, having the following structure:
15. The composition of claim 13 , wherein the immunostimulant is GLA, having the following structure:
16. The composition of claim 13 , wherein the immunostimulant is GLA, having the following structure:
17. The composition of any one of claims 15 - 16 wherein the GLA is formulated in an oil-in-water emulsion.
18. The fusion polypeptide of claim 1 , wherein ML2028 comprises the sequence of SEQ ID NO: 2 or SEQ ID NO: 4, or a sequence having at least 90% amino acid sequence identity thereto, ML2055 comprises the sequence of SEQ ID NO: 6, or a sequence having at least 90% amino acid sequence identity thereto, and ML2380 comprises the sequence of SEQ ID NO: 8, or a sequence having at least 90% amino acid sequence identity thereto.
19. The fusion polypeptide of claim 18 , further comprising M. leprae antigen ML2531, wherein ML2531 comprises the sequence of SEQ ID NO: 10, or a sequence having at least 90% amino acid sequence identity thereto.
20. A leprosy vaccine comprising a fusion polypeptide comprising Mycobacterium leprae ( M. leprae ) antigens ML2028, ML2055, and ML2380.
21. The leprosy vaccine of claim 20 , further comprising an immunostimulant.
22. The leprosy vaccine of claim 20 , wherein the immunostimulant is selected from the group consisting of a CpG-containing oligonucleotide, synthetic lipid A, monophosphoryl lipid A (MPL), saponins, saponin mimetics, amino alkyl glucosaminide 4-phosphates (AGPs), Toll-like receptor agonists, or a combination thereof.
23. The leprosy vaccine of claim 20 , wherein the immunostimulant is selected from the group consisting of a TLR4 agonist, a TLR7/8 agonist and a TLR9 agonist.
24. The leprosy vaccine of claim 20 , wherein the immunostimulant is selected from the group consisting of glucopyranosyl lipid A (GLA), CpG-containing oligonucleotide, imiquimod, gardiquimod and resiquimod.