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 variant factor H binding protein (fHbp), wherein the variant fHbp comprises:
an amino acid sequence at least 90% identical to the entire length of the amino acid sequence of fHbp ID 22 set forth in SEQ ID NO:2; and
an amino acid substitution of glycine at position 220 (G220), relative to the amino acid sequence set forth in SEQ ID NO:2, wherein the numbering of G220 is based on the numbering of amino acid residues in SEQ ID NO:1.
2. The variant fHbp of claim 1 , wherein the variant comprises the amino acid substitution G220S, G220N, G220Q, G220D, G220E, G220K, G220R, G220H, G220F, G220Y, or G220W.
3. The variant fHbp of claim 1 , further comprising the following substitutions: L130R and G133D.
4. The variant fHbp of claim 1 , comprising the substitutions: L130R, G133D, and G220S.
5. The variant fHbp of claim 1 , wherein the variant fHbp differs from the sequence of SEQ ID NO: 2 by 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids.
6. The variant fHbp of claim 1 , wherein the amino acid sequence of the variant fHbp is at least 95% identical to the entire length of the amino acid sequence set forth in SEQ ID NO:2.
7. The variant fHbp of claim 1 , wherein the amino acid sequence of the variant fHbp is at least 98% identical to the entire length of the amino acid sequence set forth in SEQ ID NO:2.
8. An immunogenic composition comprising:
a) the variant fHbp according to claim 1 ; and
b) a pharmaceutically acceptable excipient.
9. The immunogenic composition of claim 8 , wherein the variant fHbp is in a vesicle preparation prepared from a Neisseria meningitidis.
10. The immunogenic composition of claim 9 , wherein the pharmaceutically acceptable excipient comprises an adjuvant.
11. The immunogenic composition of claim 10 , wherein the adjuvant is aluminum phosphate.
12. The immunogenic composition of claim 10 , wherein the adjuvant is aluminum hydroxide.
13. The immunogenic composition of claim 8 , further comprising Neisserial surface protein A.
14. A method of eliciting an antibody response to Neisseria meningitidis in a mammal, the method comprising administering to the mammal an immunologically effective amount of the immunogenic composition of claim 8 .
15. The method of claim 14 , wherein the mammal is a human.
16. A method of eliciting an antibody response to Neisseria meningitidis in a mammal, the method comprising administering to the mammal an immunologically effective amount of the immunogenic composition of claim 9 .
17. The method of claim 15 , wherein the mammal is a human.