Modified meningococcal FHBP polypeptides

Patent metadata

Field	Value
Publication number	US-11021522-B2
Application number	US-201916458365-A
Country	US
Kind code	B2
Filing date	Jul 1, 2019
Priority date	Feb 28, 2014
Publication date	Jun 1, 2021
Grant date	Jun 1, 2021

Abstract

Modified meningococcal fHbp polypeptides with increased stability.

First claim

The invention claimed is:

1. A mutant v3 fHbp polypeptide comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 17 and containing an amino acid residue corresponding to residue S32 of SEQ m NO: 17 that has been substituted with any other amino acid, and further comprising a substitution at a position corresponding to L126 of SEQ ID NO: 17.

2. The polypeptide of claim 1 , comprising:
(a) a sequence that differs from SEQ ID NO: 17 only by substitution at the position corresponding to S32 and at a position corresponding to L126; or
(b) a sequence that differs from SEQ ID NO: 17 only by substitutions of 532V and L126R.

3. The polypeptide of claim 1 , haying a sequence comprising: substitutions S32V and L126R.

4. A mutant v3 fHbp polypeptide comprising a sequence selected from:
(a) SEQ ID NO: 44,
(b) SEQ ID NO: 44 with 1, 2, 3, 4, or 5 single amino acid substitutions, deletions and/or insertions at positions other than residue V32 and R126, wherein the polypeptide can elicit antibodies which bind to a wild-type v 3 meningococcal fHbp polypeptide consisting of the amino acid sequence of SEQ ID NO: 40; and
(c) a wild-type v 3 fHbp amino acid sequence having at least 90% sequence identity to SEQ ID NO: 17 that has been mutated at the amino acid position corresponding to Leu-126 of SEQ ID NO: 17, provided that the mutation is not a substitution to alanine.

5. An immunogenic composition comprising a polypeptide of claim 1 .

6. The composition of claim 5 , further comprising a second polypeptide that, when administered to a mammal, elicits an antibody response that is bactericidal against meningococcus.

7. The composition of claim 5 , further comprising a conjugated capsular saccharide selected from (i) a conjugated capsular saccharide from N. meningitidis serogroup A, C, W135 or Y, and (ii) a conjugated capsular saccharide from S. pneumoniae.

8. A method for raising an antibody response in a mammal, comprising administering an immunogenic composition of claim 5 to said mammal.

9. The polypeptide of claim 2 , comprising a sequence that differs from SEQ. ID NO: 17 only by substitutions of S32V and L126R.

10. An immunogenic composition comprising a polypeptide of claim 4 .

Assignees

• Glaxosmithkline Biologicals Sa

Inventors

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

Classifications

• C12N2800/101

  for bacteria · CPC title

• C12N15/74

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

• C07K14/22 Primary

  from Neisseriaceae (F) · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61K2039/70

  Multivalent vaccine · CPC title