Chimeric OspA genes, proteins, and methods of use thereof
View Patent ↗The invention relates to the development of chimeric OspA molecules for use in a new Lyme vaccine. More specifically, the chimeric OspA molecules comprise the proximal portion from one OspA serotype, together with the distal portion from another OspA serotype, while retaining antigenic properties of both of the parent polypeptides. The chimeric OspA molecules are delivered alone or in combination to provide protection against a variety of Borrelia genospecies. The invention also provides methods for administering the chimeric OspA molecules to a subject in the prevention and treatment of Lyme disease or borreliosis.
1. A polypeptide selected from the group consisting of:
(a) a polypeptide comprising an amino acid sequence having at least 95 percent sequence identity to the amino acid sequence set forth in SEQ ID NO: 173;
(b) a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 173; and
(c) a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 173.
2. The polypeptide of claim 1 further comprising an N-terminal outer surface protein B (OspB) polypeptide fragment of Borrelia , wherein the OspB polypeptide fragment comprises an OspB leader sequence.
3. A composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable carrier.
4. The composition of claim 3 further comprising an additional polypeptide from an outer surface protein A (OspA) protein of Borrelia.
5. The composition of claim 4 , wherein Borrelia is Borrelia burgdorferi, Borrelia afzelii, Borrelia garinii, Borrelia japonica, Borrelia andersonii, Borrelia bissettii, Borrelia sinica, Borrelia turdi, Borrelia tanukii, Borrelia valaisiana, Borrelia lusitaniae, Borrelia spielmanii, Borrelia miyamotoi or Borrelia lonestar.
6. The composition of claim 4 , wherein the additional polypeptide is a chimeric polypeptide selected from the group consisting of:
(a) a polypeptide comprising an amino acid sequence having at least 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99 percent sequence identity to the amino acid sequence of SEQ ID NO: 171;
(b) a polypeptide comprising the amino acid sequence of SEQ ID NO: 171;
(c) a polypeptide consisting of the amino acid sequence of SEQ ID NO: 171;
(d) a polypeptide comprising an amino acid sequence having at least 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99 percent sequence identity to the amino acid sequence of SEQ ID NO: 169;
(e) a polypeptide comprising the amino acid sequence of SEQ ID NO: 169; and
(f) a polypeptide consisting of the amino acid sequence of SEQ ID NO: 169.
7. The composition of claim 6 , wherein the additional polypeptide is a chimeric polypeptide having at least 85% sequence identity to SEQ ID NO:171.
8. The composition of claim 7 , wherein the additional polypeptide is a chimeric polypeptide having at least 90% sequence identity to SEQ ID NO:171.
9. The composition of claim 8 , wherein the additional polypeptide is a chimeric polypeptide having at least 95% sequence identity to SEQ ID NO:171.
10. The composition of claim 6 , wherein the additional polypeptide is a chimeric polypeptide having at least 85% sequence identity to SEQ ID NO:169.
11. The composition of claim 10 , wherein the additional polypeptide is a chimeric polypeptide having at least 90% sequence identity to SEQ ID NO:169.
12. The composition of claim 11 , wherein the additional polypeptide is a chimeric polypeptide having at least 95% sequence identity to SEQ ID NO:169.
13. The composition of claim 4 , wherein the additional polypeptide further comprises an N-terminal outer surface protein B (OspB) polypeptide fragment of Borrelia , wherein the OspB polypeptide fragment comprises an OspB leader sequence.
14. The composition of claim 4 comprising at least three polypeptides, wherein the polypeptides have different sequences.
15. The composition of claim 14 , wherein the polypeptides individually comprise the amino acid sequences set forth in SEQ ID NOS: 169, 171, and 173.
16. The polypeptide of claim 1 comprising an amino acid sequence having at least 96 percent sequence identity to the amino acid sequence set forth in SEQ ID NO: 173.
17. The polypeptide of claim 1 comprising an amino acid sequence having at least 97 percent sequence identity to the amino acid sequence set forth in SEQ ID NO: 173.
18. The polypeptide of claim 1 comprising an amino acid sequence having at least 98 percent sequence identity to the amino acid sequence set forth in SEQ ID NO: 173.
19. The polypeptide of claim 1 comprising an amino acid sequence having at least 99 percent sequence identity to the amino acid sequence set forth in SEQ ID NO: 173.
20. The polypeptide of claim 1 comprising an amino acid sequence having at least 95 percent sequence identity to the amino acid sequence set forth in SEQ ID NO: 173.
21. The polypeptide of claim 1 comprising the amino acid sequence set forth in SEQ ID NO: 173.
22. The polypeptide of claim 1 consisting of the amino acid sequence set forth in SEQ ID NO: 173.
23. The polypeptide of any one of claims 16 - 22 further comprising an N-terminal outer surface protein B (OspB) polypeptide fragment of Borrelia , wherein the OspB polypeptide fragment comprises an OspB leader sequence.
24. A composition comprising the polypeptide of any one of claims 16 - 22 and a pharmaceutically acceptable carrier.
25. The composition of claim 24 further comprising an additional polypeptide from an outer surface protein A (OspA) protein of Borrelia.
26. The composition of claim 25 , wherein Borrelia is Borrelia burgdorferi, Borrelia afzelii, Borrelia garinii, Borrelia japonica, Borrelia andersonii, Borrelia bissettii, Borrelia sinica, Borrelia turdi, Borrelia tanukii, Borrelia valaisiana, Borrelia lusitaniae, Borrelia spielmanii, Borrelia miyamotoi or Borrelia lonestar.
27. The composition of claim 25 , wherein the additional polypeptide is a chimeric polypeptide selected from the group consisting of:
(a) a polypeptide comprising an amino acid sequence having at least 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99 percent sequence identity to the amino acid sequence of SEQ ID NO: 171;
(b) a polypeptide comprising the amino acid sequence of SEQ ID NO: 171;
(c) a polypeptide consisting of the amino acid sequence of SEQ ID NO: 171;
(d) a polypeptide comprising an amino acid sequence having at least 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99 percent sequence identity to the amino acid sequence of SEQ ID NO: 169;
(e) a polypeptide comprising the amino acid sequence of SEQ ID NO: 169; and
(f) a polypeptide consisting of the amino acid sequence of SEQ ID NO: 169.
28. The composition of claim 27 , wherein the additional polypeptide is a chimeric polypeptide having at least 85% sequence identity to SEQ ID NO:171.
29. The composition of claim 28 , wherein the additional polypeptide is a chimeric polypeptide having at least 90% sequence identity to SEQ ID NO:171.
30. The composition of claim 29 , wherein the additional polypeptide is a chimeric polypeptide having at least 95% sequence identity to SEQ ID NO:171.
31. The composition of claim 27 , wherein the additional polypeptide is a chimeric polypeptide having at least 85% sequence identity to SEQ ID NO:169.
32. The composition of claim 31 , wherein the additional polypeptide is a chimeric polypeptide having at least 90% sequence identity to SEQ ID NO:169.
33. The composition of claim 32 , wherein the additional polypeptide is a chimeric polypeptide having at least 95% sequence identity to SEQ ID NO:169.
34. The composition of claim 25 comprising at least three polypeptides, wherein the polypeptides have different sequences.
35. The composition of claim 34 , wherein the polypeptides individually comprise the amino acid sequences set forth in SEQ ID NOS: 169, 171, and 173.