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:
the amino acid sequence of fHbp ID 55 set forth in SEQ ID NO:3, wherein the histidine at position 248 (H248) is substituted with L, I, V, D, E, F, Y, or W, and wherein the numbering of the position H248 is based on the numbering of amino acid residues in SEQ ID NO:1.
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. 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 .
5. The method of claim 4 , wherein the mammal is a human.
6. 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 3 .
7. The method of claim 6 , wherein the mammal is a human.
8. The variant fHbp according to claim 1 , comprising the substitution H248L.
9. The immunogenic composition of claim 2 , wherein said pharmaceutically acceptable excipient comprises an adjuvant.
10. The immunogenic composition of claim 9 , wherein the adjuvant is aluminum phosphate or aluminum hydroxide.
11. The immunogenic composition of claim 9 , wherein the adjuvant is an oil-in-water emulsion.
12. The immunogenic composition of claim 9 , wherein the adjuvant is monophosphoryl lipid A.
13. The immunogenic composition of claim 9 , wherein the adjuvant is saponin.
14. The immunogenic composition of claim 2 , further comprising Neisserial surface protein A.
15. An in vitro host cell expressing the variant fHbp according to claim 1 .
16. The in vitro host cell according to claim 15 , wherein the host cell is Escherichia coli.
17. The in vitro host cell according to claim 15 , wherein the host cell is yeast.
18. The in vitro host cell according to claim 15 , wherein the host cell is Neisseria meningitidis.
19. The in vitro host cell according to claim 18 , wherein the Neisseria meningitidis comprises a genetic modification that results in decreased or no toxic activity of lipid A.