Factor H binding proteins (FHBP) with altered properties and methods of use thereof
View Patent ↗Factor H binding proteins that can elicit antibodies that are bactericidal for at least one strain of N. meningitidis , and methods of use of such proteins, are provided.
1. A non-naturally occurring factor H binding protein (fHbp) comprising the amino acid sequence of SEQ ID NO:1, wherein the arginine present at position 41 (R41) in SEQ ID NO:1 is substituted with serine.
2. The non-naturally occurring fHbp of claim 1 , wherein the non-naturally occurring fHbp binds human factor H (fH) with an affinity that is no more than 45% of the affinity of fHbp ID1 for the human fH, wherein the fHbp ID1 has the amino acid sequence of SEQ ID NO: 1.
3. The non-naturally occurring fHbp of claim 1 , wherein the non-naturally occurring fHbp, when administered to a mammal, elicits antibodies bactericidal to Neisseria meningitidis ( N. meningitidis ) at a titer comparable to antibodies bactericidal to the N. meningitidis elicited by administration of fHbp ID1 to the mammal, wherein the fHbp ID1 has the amino acid sequence of SEQ ID NO: 1.
4. The non-naturally occurring fHbp of claim 1 , wherein the non-naturally occurring fHbp, when administered to a mammal, elicits antibodies bactericidal to Neisseria meningitidis ( N. meningitidis ) at a titer higher than antibodies bactericidal to the N. meningitidis elicited by administration of the fHbp ID1 to the mammal, wherein the fHbp ID1 has the amino acid sequence of SEQ ID NO: 1.
5. An immunogenic composition comprising:
a) the non-naturally occurring fHbp according to claim 1 ; and
b) a pharmaceutically acceptable excipient.
6. The immunogenic composition of claim 5 , wherein the non-naturally occurring fHbp is in a vesicle preparation prepared from a Neisseria meningitidis strain.
7. The immunogenic composition of claim 5 , wherein the pharmaceutically acceptable excipient comprises an adjuvant.
8. The immunogenic composition of claim 7 , wherein the adjuvant is aluminum hydroxide.
9. The immunogenic composition of claim 7 , wherein the adjuvant is aluminum phosphate.
10. The immunogenic composition of claim 7 , wherein the adjuvant is an oil-in-water emulsion.
11. The immunogenic composition of claim 7 , wherein the adjuvant is monophosphoryl lipid A.
12. The immunogenic composition of claim 7 , wherein the adjuvant is saponin.
13. The immunogenic composition of claim 7 , further comprising Neisserial surface protein A (NspA).
14. A method of eliciting an antibody response against Neisseria meningitidis in a mammal, the method comprising administering to a mammal the immunogenic composition of claim 5 .
15. The method of claim 14 , wherein said mammal is a human.