Combinations of meningococcal factor H binding proteins

Patent metadata

Field	Value
Publication number	US-10478483-B2
Application number	US-201113806743-A
Country	US
Kind code	B2
Filing date	Jun 24, 2011
Priority date	Jun 25, 2010
Publication date	Nov 19, 2019
Grant date	Nov 19, 2019

Abstract

The M01573 sequence of meningococcal fHbp offers poor coverage in a vaccine. The invention addresses this poor coverage in two ways. In a first aspect, a fHbp-based vaccine includes two family I fHbp sequences, one which is more closely related to MC58 than to M01573, and vice versa. In a second aspect, a multi-family fHbp-based vaccine uses a family I fHbp sequence which is more closely related to MC58 than to M01573, in combination with a family III fHbp sequence.

First claim

The invention claimed:

1. An immunogenic composition which comprises an immunologically effective amount of an adjuvant, an immunologically effective amount of a first isolated factor H binding protein (fHbp) antigen and an immunologically effective amount of a second isolated fHbp antigen, wherein: the first isolated fHbp antigen comprises a first amino acid sequence which has at least 75% sequence identity to both of SEQ ID NO: 1 and SEQ ID NO: 23, but the first amino acid sequence has a higher sequence identity to SEQ ID NO: 1 than to SEQ ID NO: 23, when aligned using the same algorithm and parameters; and the second isolated fHbp antigen comprises a second amino acid sequence which has at least 75% sequence identity to both of SEQ ID NO: 1 and SEQ ID NO: 23, but the second amino acid sequence has a higher sequence identity to SEQ ID NO: 23 than to SEQ ID NO: 1, when aligned using the same algorithm and parameters.

2. An immunogenic composition which comprises an immunologically effective amount of an adjuvant, an immunologically effective amount of a first isolated fHbp antigen and an immunologically effective amount of a second isolated fHbp antigen, wherein: the first isolated fHbp antigen comprises a first amino acid sequence which has at least 75% sequence identity to both of SEQ ID NO: 1 and SEQ ID NO: 23, but the first amino acid sequence has a higher sequence identity to SEQ ID NO: 1 than to SEQ ID NO: 23, when aligned using the same algorithm and parameters; and the second isolated fHbp antigen comprises a second amino acid sequence (i) having at least 94% sequence identity to SEQ ID NO: 25 and/or (ii) consisting of a fragment of at least 50 contiguous amino acids from SEQ ID NO: 25.

3. The composition of claim 1 , wherein the first isolated fHbp antigen can elicit antibodies in a mouse which are bactericidal against strain MC58 in a serum bactericidal assay.

4. The composition of claim 2 , wherein the first isolated fHbp antigen can elicit antibodies in a mouse which are bactericidal against strain MC58 in a serum bactericidal assay.

5. The composition of claim 2 , wherein the second isolated fHbp antigen can elicit antibodies in a mouse which are bactericidal against strain 961-5945 in a serum bactericidal assay.

6. The composition of claim 1 , wherein the second isolated fHbp antigen elicits antibodies in a mouse which are not bactericidal against strain MC58 in a serum bactericidal assay.

7. The composition of claim 1 , including a third isolated fHbp antigen comprising an amino acid sequence (i) having at least 94% sequence identity to SEQ ID NO: 25 and/or (ii) consisting of a fragment of at least 50 contiguous amino acids from SEQ ID NO: 25.

8. The composition of claim 7 , wherein the third isolated fHbp antigen can elicit antibodies in a mouse which are bactericidal against strain 961-5945 in a serum bactericidal assay.

9. The composition of claim 2 , wherein the composition does not include (i) an antigen comprising an amino acid sequence which has >95% sequence identity to SEQ ID NO: 23 or (ii) an antigen comprising an amino acid sequence which has >95% sequence identity to SEQ ID NO: 24.

10. The composition of claim 1 , wherein the adjuvant includes an aluminium salt.

Assignees

• Aricò Maria
• Brunelli Brunella
• Comanducci Maurizio
• Pizza Mariagrazia
• Savino Silvana
• Scarselli Maria
• Glaxosmithkline Biologicals Sa

Inventors

• Aricò Maria
• Brunelli Brunella
• Comanducci Maurizio
• Pizza Mariagrazia
• Savino Silvana
• Scarselli Maria

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• A61K2039/55505

  Inorganic adjuvants · CPC title

• A61K2039/70

  Multivalent vaccine · CPC title

• A61K39/385

  Haptens or antigens, bound to carriers · CPC title

• A61K39/095 Primary

  Neisseria · CPC title