CC-chemokine binding tick proteins
View Patent ↗A novel CC-chemokine binding protein is isolated from the saliva of Rhipicephalus sanguineus . Compounds prepared in accordance with the present invention can be used as anti-inflammatory and immunomodulatory compounds and in the treatment or prevention of CC-chemokine-related diseases.
1. An isolated polypeptide that:
a) comprises SEQ ID NO: 5;
b) comprises SEQ ID NO: 6; or
c) a fusion protein comprising any one of a) or b) operably linked to a heterologous sequence selected from an extracellular domain of a membrane-bound protein, an immunoglobulin constant region, a multimerization domain, a heterodimeric protein hormone, a signal peptide, an export signal, or a tag sequence.
2. The isolated polypeptide of claim 1 , wherein said polypeptide is post-translationally modified.
3. The isolated polypeptide of claim 2 , wherein said polypeptide is glycosylated.
4. The isolated polypeptide of claim 2 , wherein said polypeptide is PEGylated or coupled to a label or agent.
5. The isolated polypeptide of claim 1 , wherein said polypeptide hinds to a CC-chemokine selected from CCL5 or CCL11.
6. The isolated polypeptide of claim 1 , wherein said polypeptide comprises SEQ ID NO: 5.
7. The isolated polypeptide of claim 1 , wherein said polypeptide consists of SEQ ID NO: 5.
8. The isolated polypeptide of claim 1 , wherein said polypeptide comprises SEQ ID NO: 6.
9. The isolated polypeptide of claim 1 , wherein said polypeptide consists of SEQ ID NO: 6.
10. The isolated polypeptide of claim 1 , wherein said polypeptide is a fusion protein comprising SEQ ID NO: 5 operably linked to a heterologous sequence selected from an extracellular domain of a membrane-bound protein, an immunoglobulin constant region, a multimerization domain, a heterodimeric protein hormone, a signal peptide, an export signal, or a tag sequence.
11. The isolated polypeptide of claim 1 , wherein said polypeptide is a fusion protein comprising SEQ ID NO: 6 operably linked to a heterologous sequence selected from an extracellular domain of a membrane-bound protein, an immunoglobulin constant region, a multimerization domain, a heterodimeric protein hormone, a signal peptide, an export signal, or a tag sequence.
12. An isolated nucleic acid molecule encoding a polypeptide according to claim 1 .
13. The isolated nucleic acid of claim 12 , wherein said nucleic acid encodes a polypeptide comprising SEQ ID NO: 5.
14. The isolated nucleic acid of claim 12 , wherein said nucleic acid encodes a polypeptide consisting of SEQ ID NO: 5.
15. The isolated nucleic acid of claim 12 , wherein said nucleic acid encodes a polypeptide comprising SEQ ID NO: 6.
16. The isolated nucleic acid of claim 12 , wherein said nucleic acid encodes a polypeptide consisting of SEQ ID NO: 6.
17. The isolated nucleic acid of claim 12 , wherein said nucleic acid encodes a fusion protein comprising SEQ ID NO: 5 operably linked to a heterologous sequence selected from an extracellular domain of a membrane-bound protein, an immunoglobulin constant region, a multimerization domain, a heterodimeric protein hormone, a signal peptide, an export signal, or a tag sequence.
18. The isolated nucleic acid of claim 12 , wherein said nucleic acid encodes a fusion protein comprising SEQ ID NO: 6 operably linked to a heterologous sequence selected from an extracellular domain of a membrane-bound protein, an immunoglobulin constant region, a multimerization domain, a heterodimeric protein hormone, a signal peptide, an export signal, or a tag sequence.
19. The nucleic acid molecule of claim 12 , wherein said nucleic acid is a cDNA molecule.
20. The nucleic acid molecule of claim 12 , wherein said nucleic acid comprises SEQ ID NO: 3.
21. The nucleic acid molecule of claim 12 , wherein said nucleic acid comprises SEQ ID NO: 4.
22. An isolated oligonucleotide that comprises a fragment of at least 30 nucleotides of a nucleic acid molecule encoding a polypeptide of claim 1 .
23. The isolated oligonucleotide of claim 22 , wherein said oligonucleotide has a length of at least 50 nucleotides.
24. A cloning or expression vector comprising a nucleic acid molecule encoding a polypeptide of claim 1 .
25. The expression vector of claim 24 , wherein said nucleic acid molecule is operably associated with a promoter.
26. An isolated transformed host cell comprising a cloning or expression vector comprising a nucleic acid molecule encoding a polypeptide of claim 1 .
27. A process for preparing a polypeptide comprising culturing a host cell of claim 26 under conditions allowing or promoting expression of said polypeptide.
28. The process of claim 27 , further comprising purifying the protein.
29. The process of claim 27 , further comprising formulating the polypeptide into a pharmaceutical composition.
30. A pharmaceutical composition comprising a polypeptide of claim 1 .
31. A method for immunizing an animal against a blood-feeding ectoparasite, comprising administering to said animal a polypeptide of claim 1 in an amount sufficient to induce an immune response.