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 95% 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 lysine at position 219 (K219) relative to the amino acid sequence set forth in SEQ ID NO:2, wherein the numbering of K219 is based on the numbering of amino acid residues in SEQ ID NO:1,
wherein the amino acid substitution at K219 is K219N, K219Q, K219D, K219E, K219F, K219Y, or K219W.
2. An immunogenic composition comprising:
a) the variant fHbp according to claim 1 ; and
b) a pharmaceutically acceptable excipient.
3. The immunogenic composition of claim 2 , wherein the variant fHbp is in a vesicle preparation prepared from a Neisseria meningitidis strain.
4. The immunogenic composition of claim 2 , wherein said pharmaceutically acceptable excipient comprises an adjuvant.
5. The immunogenic composition of claim 2 , further comprising Neisserial surface protein A.
6. The immunogenic composition of claim 4 , wherein the adjuvant is aluminum phosphate or aluminum hydroxide.
7. A method of eliciting an antibody response to Neisseria meningitidis in a mammal, the method comprising administering to the mammal the immunogenic composition of claim 2 .
8. The method of claim 7 , wherein the mammal is a human.
9. The variant fHbp of claim 1 , wherein the amino acid substitution at K219 is K219N.
10. 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.
11. The variant fHbp of claim 1 , wherein the amino acid substitution at K219 is K219Q.
12. The variant fHbp of claim 1 , wherein the amino acid substitution at K219 is K219D.
13. The variant fHbp of claim 1 , wherein the amino acid substitution at K219 is K219E.
14. The variant fHbp of claim 1 , wherein the amino acid substitution at K219 is K219F.
15. The variant fHbp of claim 1 , wherein the amino acid substitution at K219 is K219Y.
16. The variant fHbp of claim 1 , wherein the amino acid substitution at K219 is K219W.
17. The variant fHbp of claim 10 , wherein the amino acid substitution at K219 is K219N.
18. An immunogenic composition comprising:
a) the variant fHbp according to claim 17 ; and
b) a pharmaceutically acceptable excipient.
19. The immunogenic composition of claim 18 , wherein the variant fHbp is in a vesicle preparation prepared from a Neisseria meningitidis strain.
20. A method of eliciting an antibody response to Neisseria meningitidis in a mammal, the method comprising administering to the mammal the immunogenic composition of claim 18 .
21. A method of eliciting an antibody response to Neisseria meningitidis in a mammal, the method comprising administering to the mammal the immunogenic composition of claim 19 .