FimH mutant, compositions therewith and use thereof
Polypeptides comprising a FimH lectin domain comprising 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, wherein the FimH lectin domain comprises an amino acid selected from the group consisting of valine (V), isoleucine (I), leucine (L), glycine (G), and methionine (M), at the position that corresponds to position 144 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 polypeptide comprises a mutation and wherein the mutation is the F144V substitution.
3. 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.
4. The polypeptide according to claim 1 further comprising a FimH pilin domain.
5. The polypeptide according to claim 1 , wherein the polypeptide is a full length FimH having at least 90% sequence identity with SEQ ID NO: 2.
6. A FimCH complex comprising the polypeptide according to claim 4 and FimC protein.
7. A pharmaceutical composition comprising the polypeptide according to claim 1 .
8. The pharmaceutical composition according to claim 7 , further comprising an adjuvant.
9. The polypeptide according to claim 3 , wherein the FimH lectin domain comprises SEQ ID NO: 1 wherein the phenylalanine residue at position 144 is substituted by valine.
10. The polypeptide according to claim 5 , wherein the FimH comprises SEQ ID NO: 2 wherein the phenylalanine residue at position 144 is substituted by valine.
11. A method of eliciting a humoral and/or cellular immune response in a mammalian subject comprising administering to the subject an effective amount of the pharmaceutical composition of claim 7 , wherein the humoral and/or cellular immune response is elicited to the polypeptide in the pharmaceutical composition.
12. A pharmaceutical composition comprising the polypeptide according to claim 2 .
13. A pharmaceutical composition comprising the polypeptide according to claim 3 .
14. A pharmaceutical composition comprising the polypeptide according to claim 4 .
15. A pharmaceutical composition comprising the polypeptide according to claim 5 .
16. A pharmaceutical composition comprising the FimCH complex according to claim 6 .
17. A pharmaceutical composition comprising the polypeptide according to claim 9 .
18. A pharmaceutical composition comprising the polypeptide according to claim 10 .
19. The pharmaceutical composition of claim 12 , further comprising an adjuvant.
20. The pharmaceutical composition of claim 13 , further comprising an adjuvant.
21. The pharmaceutical composition of claim 14 , further comprising an adjuvant.
22. The pharmaceutical composition of claim 15 , further comprising an adjuvant.
23. The pharmaceutical composition of claim 16 , further comprising an adjuvant.
24. The pharmaceutical composition of claim 17 , further comprising an adjuvant.
25. The pharmaceutical composition of claim 18 , further comprising an adjuvant.