Combinations of meningococcal factor H binding proteins
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.
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.