Factor H binding protein variants and methods of use thereof
View Patent ↗Variant factor H binding proteins that can elicit antibodies that are bactericidal for at least one strain of Neisseria meningitidis , compositions comprising such proteins, and methods of use of such proteins, are provided.
1. A nucleic acid encoding a variant factor H binding protein (fHbp), wherein the variant fHbp comprises: a substitution of the serine at position 223 (S223) with arginine, lysine or histidine, wherein the numbering of the position S223 is based on the numbering of amino acid residues in SEQ ID NO:1 and wherein the variant comprises an amino acid sequence having at least 85% amino acid sequence identity to SEQ ID NO:1.
2. The nucleic acid of claim 1 , wherein the substitution is S223R.
3. The nucleic acid of claim 1 , wherein the substitution is S223K.
4. The nucleic acid of claim 1 , wherein the substitution is S223H.
5. The nucleic acid of claim 1 , wherein the variant fHbp further comprises an amino acid substitution selected from the group consisting of R41S and R41A.
6. The nucleic acid of claim 1 , wherein the variant fHbp comprises an amino acid sequence having at least 90% amino acid sequence identity to SEQ ID NO:1.
7. The nucleic acid of claim 1 , wherein the variant comprises an amino acid sequence having at least 95% amino acid sequence identity to SEQ ID NO:1.
8. The nucleic acid of claim 1 , wherein the variant fHbp differs from the sequence of SEQ ID NO: 1 by 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids.
9. A recombinant expression vector comprising the nucleic acid of claim 1 .
10. An in vitro host cell comprising the nucleic acid of claim 1 .
11. The in vitro host cell of claim 10 , wherein the in vitro host cell is a prokaryotic cell.
12. The in vitro host cell of claim 11 , wherein the prokaryotic cell is a Neisseria meningitidis bacterium.
13. The in vitro host cell of claim 11 , wherein the prokaryotic cell is an Escherichia coli bacterium.
14. An in vitro host cell comprising the recombinant expression vector of claim 9 .
15. The in vitro host cell of claim 14 , wherein the in vitro host cell is a prokaryotic cell.
16. The in vitro host cell of claim 15 , wherein the prokaryotic cell is a Neisseria meningitidis bacterium.
17. The in vitro host cell of claim 15 , wherein the prokaryotic cell is an Escherichia coli bacterium.