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 an amino acid sequence, wherein the amino acid sequence is the amino acid sequence set forth in SEQ ID NO:1 but differing from the amino acid sequence of SEQ ID NO:1 by up to 7 amino acids and comprising a substitution of the arginine at position 41 with serine.
2. The non-naturally occurring fHbp of claim 1 , wherein the amino acid sequence is at least 98% identical to the amino acid sequence set forth in SEQ ID NO:1.
3. The non-naturally occurring fHbp of claim 1 , wherein the amino acid sequence is at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1.
4. An immunogenic composition comprising:
a) the fHbp according to claim 1 ; and
b) a pharmaceutically acceptable excipient.
5. The immunogenic composition of claim 4 , wherein the pharmaceutically acceptable excipient comprises an adjuvant.
6. The immunogenic composition of claim 5 , wherein the adjuvant is aluminum hydroxide, aluminum phosphate, oil-in-water emulsion, monophosphoryl lipid A, or saponin.
7. A method of eliciting an antibody response to N. meningitidis in a mammal, the method comprising administering to the mammal an immunologically effective amount of the immunogenic composition of claim 4 .
8. The method of claim 7 , wherein said mammal is a human.
9. An immunogenic composition comprising:
a) a vesicle obtained from a Neisseria meningitidis cell that is genetically modified to express a non-naturally occurring fHbp comprising an amino acid sequence, wherein the amino acid sequence is the amino acid sequence set forth in SEQ ID NO:1 but differing from the amino acid sequence of SEQ ID NO:1 by up to 7 amino acids and comprising a substitution of the arginine at position 41 with serine, wherein the vesicle comprises the non-naturally occurring fHbp; and
b) a pharmaceutically acceptable excipient.
10. The immunogenic composition of claim 9 , wherein the amino acid sequence is at least 98% identical to the amino acid sequence set forth in SEQ ID NO:1.
11. The immunogenic composition of claim 9 , wherein the amino acid sequence is at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1.
12. The immunogenic composition of claim 9 , wherein the vesicle is a native outer membrane vesicle.
13. The immunogenic composition of claim 9 , wherein the N. meningitidis cell is genetically modified to provide for decreased or no activity of a polypeptide product of the lpxL1 gene and/or the lpxL2 gene.
14. The immunogenic composition of claim 9 , wherein the N. meningitidis cell is genetically modified to provide for increased expression of its Neisserial surface protein A (NspA).
15. The immunogenic composition of claim 9 , wherein the pharmaceutically acceptable excipient comprises an adjuvant.
16. The immunogenic composition of claim 15 , wherein the adjuvant is aluminum hydroxide, aluminum phosphate, oil-in-water emulsion, monophosphoryl lipid A, or saponin.
17. A method of eliciting an antibody response to N. meningitidis in a mammal, the method comprising administering to the mammal an immunologically effective amount of the immunogenic composition of claim 9 .
18. The method of claim 17 , wherein said mammal is a human.
19. A method of eliciting a serum bactericidal antibody response against Neisseria meningitidis in a mammal, the method comprising administering to the mammal an amount of an immunogenic composition effective to elicit the bactericidal antibody response, wherein the immunogenic composition comprises a non-naturally occurring fHbp comprising the amino acid sequence set forth in SEQ ID NO: 1 but with a substitution of the arginine at its position 41 with serine.
20. A method of eliciting a serum bactericidal antibody response against Neisseria meningitidis in a mammal, the method comprising administering to the mammal an amount of an immunogenic composition comprising vesicles effective to elicit the bactericidal antibody response, wherein the vesicles are obtained from a Neisseria meningitidis cell that is genetically modified to express a non-naturally occurring fHbp comprising an amino acid sequence, wherein the amino acid sequence is the amino acid sequence set forth in SEQ ID NO: 1 but with a substitution of the arginine at its position 41 with serine.