Modified meningococcal fHbp polypeptides

Patent metadata

Field	Value
Publication number	US-12415838-B2
Application number	US-202418440212-A
Country	US
Kind code	B2
Filing date	Feb 13, 2024
Priority date	Feb 28, 2014
Publication date	Sep 16, 2025
Grant date	Sep 16, 2025

Abstract

Modified meningococcal fHbp polypeptides with increased stability.

First claim

The invention claimed is:

1. A method for preventing or for protecting against Neisserial infection in a mammal comprising administering to the mammal an immunogenic composition comprising a fusion polypeptide, wherein the fusion polypeptide comprises a mutant v2 factor H Binding Protein (fHbp) polypeptide and a mutant v3 factor H Binding Protein (fHbp) polypeptide,
(a) wherein the mutant v2 fHbp polypeptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 5 and includes an amino acid residue corresponding to residue 32 of SEQ ID NO: 5, wherein the amino acid sequence of the mutant v2 fHbp polypeptide differs from SEQ ID NO: 5 at residue 32 by the substitution S32V, and/or
(b) wherein the mutant v3 fHbp polypeptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 17 and includes an amino acid residue corresponding to residue 32 from SEQ ID NO: 17, wherein the amino acid sequence of the mutant v3 fHbp polypeptide differs from SEQ ID NO: 17 at residue 32 by the substitution S32V.

2. The method of claim 1 , wherein the mutant v2 fHbp polypeptide further differs from SEQ ID NO: 5 by substitution at one or more of L123, V124, S125, G126, L127 and/or G128.

3. The method of claim 2 , wherein the substitution(s) are selected from the group consisting of: L123R; V124I; S125G or S125T; G126D; L127I; and G128A.

4. The method of claim 1 , wherein the mutant v2 fHbp polypeptide further comprises a L123 mutation.

5. The method of claim 4 , wherein the L123 mutation is a L123R mutation.

6. The method of claim 1 , wherein the mutant v3 fHbp polypeptide further differs from SEQ ID NO: 17 by substitution at one or more of S32, I33, L39, L41, F72, V103, T116, F125, L126, V127, S128, G129, L130, G131, S154, H242, and/or E243.

7. The method of claim 6 , wherein the substitution(s) are selected from the group consisting of: I33C, L39C, L41C, F72C, V103T, T116S, F125C, L126R, V127I, S128G or S128T, G129D, L130I, G131A, S154C, H242R, and E243H.

8. The method of claim 1 , wherein the mutant v3 fHbp polypeptide further comprises a L126 mutation.

9. The method of claim 8 , wherein the L126 mutation is L126R.

10. The method of claim 1 , wherein the immunogenic composition further comprises a polypeptide having the amino acid sequence of SEQ ID NO: 45; wherein SEQ ID NO: 45 is modified by up to 5 single amino acid substitutions, deletions and/or insertions; and wherein the 5 single amino acid substitutions, deletions and/or insertions do not include amino acid positions V32 and R123.

11. The method of claim 1 , wherein the immunogenic composition further comprises a polypeptide having the amino acid sequence of SEQ ID NO: 44, wherein SEQ ID NO: 44 is modified by up to 5 single amino acid substitutions, deletions and/or insertions, and wherein the 5 single amino acid substitutions, deletions and/or insertions do not include amino acid positions V32 and R126.

12. The method of claim 1 , wherein the mutant v2 fHbp polypeptide and the mutant v3 fHbp polypeptide are arranged in the order v2 fHbp polypeptide followed by v3 fHbp polypeptide from N- to C-terminus.

13. The method of claim 12 , wherein a linker having the amino acid sequence of SEQ ID NO: 50 is between the mutant v2 fHbp polypeptide and the mutant v3 fHbp polypeptide.

14. The method of claim 1 , further comprising (i) a conjugated capsular saccharide from N. meningitidis serogroup A, C, W135 and/or Y.

15. The method of claim 1 , wherein the immunogenic composition comprises the fusion polypeptide and one or more of (i) a Neisserial Heparin Binding Antigen (NHBA) polypeptide (ii) a Neisserial Adhesin (NadA) polypeptide and/or (iii) meningococcal outer membrane vesicles (OMVs).

16. The method according to claim 15 , wherein the OMVs are from a serogroup B strain.

17. The method according to claim 15 , wherein the immunogenic composition further comprises an aluminum hydroxide adjuvant.

18. The method according to claim 1 , wherein said mammal is a human.

Assignees

• Glaxosmithkline Biologicals Sa

Inventors

• Bottomley Matthew
• Malito Enrico
• Martinelli Manuele
• Scarselli Maria

Classifications

• A61K2039/70

  Multivalent vaccine · CPC title

• A61K2039/55511

  Organic adjuvants · CPC title

• A61K2039/523

  expressing foreign proteins · CPC title

• A61K39/095 Primary

  Neisseria · CPC title

• C12N15/74

  Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora · CPC title