Multiple variants of meningococcal protein NMB1870
AssigneeGlaxosmithkline Biologicals SA
InventorsMaurizio Comanducci, Mariagrazia Pizza
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Abstract
Meningococcal protein NMB 1870 has been described in the prior art. The inventors have found that NMB 1870 is an effective antigen for eliciting anti-meningococcal antibody responses, and that it is expressed across all meningococcal serogroups. Forty-two different NMB 1870 sequences have been identified, and these group into three variants. Serum raised against a given variant is bactericidal within the same variant group, but is not active against strains which express one of the other two variants i.e. there is intra-variant cross-protection, but not inter-variant cross-protection. For maximum cross-strain efficacy, therefore, the invention uses mixture comprising different variants of NMB 1870.
Claims28
A method for raising an antibody response in a mammal, comprising administering a composition comprising an aluminum salt adjuvant, a histidine buffer, and consisting of two purified antigens, wherein the two purified antigens are:
- (a) a first purified protein, comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO:
- 24;
- and (b) a second purified protein, comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO:
- 33, wherein:
- the first purified protein has less than 70% sequence identity to the second purified protein.
An immunogenic composition comprising an aluminum salt adjuvant, a histidine buffer, and consisting of two purified antigens, wherein the two purified antigens are:
- (a) a first purified protein, comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO:
- 24;
- and (b) a second purified protein, comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO:
- 33, wherein the first purified protein has less than 70% sequence identity to the second purified protein, wherein at least one of the two purified antigens is adsorbed to the aluminum salt adjuvant.
A method of preparing an immunogenic composition comprising an aluminum salt adjuvant, a histidine buffer, and consisting of two purified antigens, wherein the two purified antigens are:
- (a) a first purified protein, comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO:
- 24;
- and (b) a second purified protein, comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO:
- 33, wherein the first purified protein has less than 70% sequence identity to the second purified protein, wherein the method comprises:
- (i) separately expressing the antigens in E. coli;
- (ii) purifying the antigens from the E. coli;
- (iii) mixing the antigens;
- and
- (iv) formulating the immunogenic composition.
A method of formulating an immunogenic composition comprising an aluminum salt adjuvant, a histidine buffer, and consisting of two purified antigens, wherein the two purified antigens are:
- (a) a first purified protein, comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO:
- 24;
- and (b) a second purified protein, comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO:
- 33, wherein the first purified protein has less than 70% sequence identity to the second purified protein, wherein the method comprises:
- (i) mixing the antigens;
- and
- (ii) formulating the immunogenic composition.
Dependencies are inferred from the claim text.