Chimeric OspA genes, proteins and methods of use thereof
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. An isolated polypeptide comprising an amino acid sequence having at least about 90 percent sequence identity to the amino acid sequence set forth in SEQ ID NO: 12, wherein the polypeptide maintains the following mutations: methionine (M) at amino acid 121, tyrosine (Y) at amino acid 142, and methionine (M) at amino acid 172.
2. A composition comprising the isolated polypeptide of claim 1 and a pharmaceutically acceptable carrier.
3. The composition of claim 2 , wherein the composition further comprises at least one additional polypeptide comprising an amino acid sequence having at least about 85 percent sequence identity to an amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:4, or SEQ ID NO: 6, SEQ ID NO: 8, or SEQ ID NO: 10.
4. An immunogenic composition comprising the composition of claim 2 and an adjuvant.
5. The composition of claim 2 , in combination with at least a second composition.
6. The composition of claim 5 wherein the second composition protects against a tick-borne disease.
7. The composition of claim 6 wherein the tick-borne disease is Rocky Mountain Spotted Fever, Babesiosis, Relapsing Fever, Colorado tick fever, Human monocytic ehrlichiosis (HME), Human granulocytic ehrlichiosis (HGE), Southern Tick-Associated Rash Illness (STARI), Tularemia, Tick paralysis, Powassan encephalitis, Q fever, Crimean-Congo hemorrhagic fever, Cytauxzoonosis, boutonneuse fever, or tick-borne encephalitis.
8. The composition of claim 6 wherein the second composition is a tick-borne encephalitis vaccine.
9. A method for inducing an immunological response in a subject, the method comprising the step of administering the composition of claim 2 to the subject in an amount effective to induce an immunological response.
10. The method of claim 9 wherein the immunological response comprises production of an anti-OspA antibody and wherein the isolated polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 12.
11. A composition comprising at least two of the isolated polypeptides of claim 1 and a pharmaceutically acceptable carrier, wherein the polypeptides have different sequences.
12. The isolated polypeptide of claim 1 comprising an amino acid sequence having at least 91 percent sequence identity to the amino acid sequence set forth in SEQ ID NO: 12.
13. The isolated polypeptide of claim 1 comprising an amino acid sequence having at least 92 percent sequence identity to the amino acid sequence set forth in SEQ ID NO: 12.
14. The isolated polypeptide of claim 1 comprising an amino acid sequence having at least 93 percent sequence identity to the amino acid sequence set forth in SEQ ID NO: 12.
15. The isolated polypeptide of claim 1 comprising an amino acid sequence having at least 94 percent sequence identity to the amino acid sequence set forth in SEQ ID NO: 12.
16. The isolated 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: 12.
17. The isolated 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: 12.
18. The isolated 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: 12.
19. The isolated 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: 12.
20. The isolated 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: 12.
21. An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 12.
22. The isolated polypeptide of claim 21 , wherein the polypeptide consists of the amino acid sequence set forth in SEQ ID NO: 12.
23. A composition comprising the isolated polypeptide of claim 21 and a pharmaceutically acceptable carrier.
24. An immunogenic composition comprising the composition of claim 23 and an adjuvant.