FimH mutants, compositions therewith and use thereof
Polypeptides comprising a FimH lectin domain comprising at least one an amino acid mutation that causes the FimH lectin domain to be in the low affinity conformation for mannose are described. Pharmaceutical compositions which comprise such polypeptides and methods of stimulating an immune response in a subject in need thereof by administration of the polypeptide are further described.
1. A polypeptide comprising a FimH lectin domain comprising Tyrosine (Y) or Tryptophan (W) at the position that corresponds to position 71 in SEQ ID NO: 1, wherein the FimH lectin domain has an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 1.
2. The polypeptide according to claim 1 , wherein the FimH lectin domain comprises Tyrosine (Y) at the position that corresponds to position 71 in SEQ ID NO: 1.
3. The polypeptide according to claim 1 , wherein the polypeptide further comprises an amino acid other than phenylalanine (F) at a position corresponding to position 144 in the amino acid sequence of SEQ ID NO: 1.
4. The polypeptide according to claim 3 , wherein the polypeptide comprises an amino acid selected from the group consisting of valine (V), isoleucine (I), leucine (L), glycine (G), methionine (M), and alanine (A) at the position that corresponds to position 144 in SEQ ID NO: 1.
5. The polypeptide according to claim 3 , wherein the FimH lectin domain comprises Valine (V) at the position that corresponds to position 144 in SEQ ID NO: 1.
6. The polypeptide according to claim 1 , wherein the FimH lectin domain has an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 1.
7. The polypeptide according to claim 6 , wherein the FimH lectin domain comprises SEQ ID NO: 1 wherein the phenylalanine residue at position 71 is substituted by tyrosine and wherein the phenylalanine residue at position 144 is substituted by valine.
8. The polypeptide according to claim 1 , wherein the polypeptide further comprises a FimH pilin domain.
9. The polypeptide according to claim 6 , wherein the polypeptide is a full length FimH having at least 90% sequence identity with SEQ ID NO: 2.
10. A pharmaceutical composition comprising the polypeptide according to claim 1 .
11. The polypeptide of claim 6 , wherein the FimH lectin domain comprises SEQ ID NO: 1 wherein the phenylalanine residue at position 71 is substituted by tyrosine.
12. The polypeptide of claim 9 , wherein the FimH lectin domain comprises SEQ ID NO: 2 wherein the phenylalanine residue at position 71 is substituted by tyrosine and the phenylalanine residue at position 144 is substituted by valine.
13. A pharmaceutical composition comprising the polypeptide of claim 2 .
14. A pharmaceutical composition comprising the polypeptide of claim 3 .
15. A pharmaceutical composition comprising the polypeptide of claim 4 .
16. A pharmaceutical composition comprising the polypeptide of claim 5 .
17. A pharmaceutical composition comprising the polypeptide of claim 6 .
18. A pharmaceutical composition comprising the polypeptide of claim 7 .
19. A pharmaceutical composition comprising the polypeptide of claim 8 .
20. A pharmaceutical composition comprising the polypeptide of claim 9 .
21. A pharmaceutical composition comprising the polypeptide of claim 11 .
22. A pharmaceutical composition comprising the polypeptide of claim 12 .
23. The pharmaceutical composition of claim 13 , further comprising an adjuvant.
24. The pharmaceutical composition of claim 14 , further comprising an adjuvant.
25. The pharmaceutical composition of claim 15 , further comprising an adjuvant.
26. The pharmaceutical composition of claim 16 , further comprising an adjuvant.
27. The pharmaceutical composition of claim 17 , further comprising an adjuvant.
28. The pharmaceutical composition of claim 18 , further comprising an adjuvant.
29. The pharmaceutical composition of claim 19 , further comprising an adjuvant.
30. The pharmaceutical composition of claim 20 , further comprising an adjuvant.
31. The pharmaceutical composition of claim 21 , further comprising an adjuvant.
32. The pharmaceutical composition of claim 22 , further comprising an adjuvant.
33. The pharmaceutical composition of claim 23 , further comprising an adjuvant.