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1. (WO2018042178) MODIFIED FACTOR H BINDING PROTEIN
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CLAIMS

1. A modified factor H binding protein (fHbp), comprising fHbp, or a variant thereof, modified with the addition of at least one exogenous peptide loop.

2. The modified factor H binding protein according to claim 1 , wherein the fHbp is meningococcal or gonococcal fHbp, or a variant thereof.

3. The modified factor H binding protein according to claim 1 or claim 2, wherein the modified fHbp is modified such that it is not capable of binding factor H, or at least has reduced factor H binding activity.

4. The modified factor H binding protein according to any preceding claim, wherein the exogenous peptide loop(s) is immunogenic.

5. The modified factor H binding protein according to any preceding claim, wherein the exogenous peptide loop(s) is derived from an integral outer membrane protein.

6. The modified factor H binding protein according to any preceding claim, wherein the exogenous peptide loop(s) is prokaryotic in origin.

7. The modified factor H binding protein according to any preceding claim, wherein the exogenous peptide loop(s) is derived from a membrane protein.

8. The modified factor H binding protein according to any preceding claim, wherein the exogenous peptide loop(s) is derived from a meningococcal protein.

9. The modified factor H binding protein according to any preceding claim, wherein the exogenous peptide loop(s) is derived from a gonococcal protein.

10. The modified factor H binding protein according to any preceding claim, wherein the exogenous peptide loop(s) comprise a fragment of PorA, or a variant thereof.

1 1. The modified factor H binding protein according to any preceding claim, wherein the exogenous peptide loop(s) are between 8 and 20 amino acids in length.

12. The modified factor H binding protein according to any preceding claim, wherein the exogenous peptide loop(s) are about 16 amino acids in length.

13. The modified factor H binding protein according to any preceding claim, wherein the exogenous peptide loop(s) are selected from any one of the PorA loops 1 to 7, or fragments thereof; and/or variants thereof; and/or combinations thereof; or

wherein the exogenous peptide loop(s) are selected from any one of the PorA loops provided in Table 1 herein (e.g. any of SEQ ID NOs: 45 to 79), or variant thereof.

14. The modified factor H binding protein according to any preceding claim, wherein the modified fHbp comprises two or more exogenous peptide loops.

15. The modified factor H binding protein according to any preceding claim, wherein the modified fHbp comprises between 1 and 7 exogenous peptide loops.

16. The modified factor H binding protein according to any preceding claim, wherein the modified fHbp, or variant thereof, is modified with an exogenous peptide loop in at least two positions.

17. The modified factor H binding protein according to any preceding claim, wherein the peptide loop is inserted into fHbp, or a variant thereof, at one or more of amino acid positions selected from 49-54, 83-88, 1 14- 124, 199-206, 227-233, and 240-246.

18. The modified factor H binding protein according to any preceding claim, wherein the modified fHbp is immunogenic.

19. The modified factor H binding protein according to any preceding claim, wherein the modified fHbp is a fusion protein.

20. The modified factor H binding protein according to any preceding claim, wherein the modified fHbp comprises the sequence of any one of SEQ ID NOs: 1 to 13 ; or a variant thereof.

21. A nucleic acid encoding the modified fHbp according to any of claims 1 to 20.

22. The nucleic acid according to claim 21 , wherein the nucleic acid is a vector, optionally a viral vector.

23. A composition comprising the modified fHbp according to any of claims 1 to 10 or the nucleic acid according to claims 21 or 22.

24. The composition according to claim 23, wherein the composition comprises two or more different modified fHbp molecules.

25. The composition according to claim 23 or claim 24, wherein the composition comprises a pharmaceutically acceptable carrier.

26. The composition according to any of claims 23 to 25, wherein the composition further comprises an adjuvant.

27. The composition according to any of claims 23 to 26, wherein the composition further comprises at least one other prophylactically or therapeutically active molecule; and optionally

wherein the at least one other prophylactically or therapeutically active molecule comprises:

a monovalent proteinxapsule polysaccharide vaccine; or

a conjugate vaccine, wherein antigen(s) comprising the fHbp scaffold bearing exogenous peptide loops is incorporated as the protein carrier molecule in the conjugate vaccine.

28. A modified fHbp according to any of claims 1 to 20, a nucleic acid according to claim 20 or 21 , or a composition according to any of claims 23 to 27, for use as a medicament.

29. A modified fHbp according to any of claims 1 to 20, a nucleic acid according to claim 21 or 22, or a composition according to any of claims 23 to 27, for use in the treatment or prevention of a pathogenic infection or colonisation of a subject.

30. A method of treatment or prevention of a pathogenic infection or colonisation of a subj ect, comprising the administration of a modified fHbp according to any of claims 1 to 20, a nucleic acid according to claim 21 or 22, or a composition according to any of claims 23 to 27, to the subj ect.

3 1. A method of vaccination, comprising the administration of a modified fHbp according to any of claims 1 to 20, a nucleic acid according to claim 21 or 22, or a composition according to any of claims 23 to 27, to a subj ect.

32. A combination of the modified fHbp according to any of claims 1 to 20, a nucleic acid according to claim 21 or 22, or a composition according to any of claims 23 to 27 and at least one other prophylactically or therapeutically active molecule.

33. The combination according to claim 32, wherein at least one other prophylactically or therapeutically active molecule comprises a monovalent proteinxapsule polysaccharide vaccine.

34. The combination according to claim 33 or composition according to claim 26, wherein the monovalent proteinxapsule polysaccharide vaccine comprises any of serogroup C or A capsule with bacterial toxoids, bi-valent vaccines (with serogroup C and A capsular polysaccharide conjugated to bacterial toxoids), quadri- (serogroups A, C, Y, W) or penta- (A, C, Y, W, X) valent conjugate vaccines.

35. The combination according to claim 32 or composition according to claim 26, wherein the at least one other prophylactically or therapeutically active molecule comprises a conjugate vaccine, wherein antigen(s) comprising the fHbp scaffold bearing exogenous peptide loops is incorporated as the protein carrier molecule in the conjugate vaccine, optionally wherein the conjugate vaccine comprises any of serogroup capsular polysaccharides selected from A, C, Y, W, or X strains, or combinations thereof.

36. Use of factor H binding protein (fHbp) as an epitope display scaffold.

37. The modified fHbp, nucleic acid, composition, method or use essentially as described herein, optionally with reference to the accompanying figures.