Factor H Binding Proteins (FHBP) with Altered Properties and Methods of Use Thereof
AssigneeChildren's Hospital & Research Center Oakland
InventorsPETER T. BEERNINK, DAN M. GRANOFF, ROLANDO PAJON FEYT
Life of this patent
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Abstract
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.
Claims48
A non-naturally occurring factor H binding protein (fHbp) that has lower affinity for human factor H (1H) than fHbp ID 1, wherein said non-naturally occurring fHbp presents a conformational epitope bound by antibodies that have bactericidal activity toward at least one Neisseria meningitidis strain.
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An immunogenic composition comprising:
- a) an isolated factor H binding protein (fHbp) comprising at least 85% amino acid sequence identity to fHbp ID 4, fHbp ID 14, fHbp ID 15, wherein said fHbp has lower affinity for human factor H (1H) than fHbp ID 1;
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- b) a pharmaceutically acceptable excipient.
A method of determining the likelihood that a factor H binding protein (fHbp) will elicit a bactericidal response in an individual to at least one Neisseria meningitidis strain, the method comprising:
- determining the ability of antibody, present in serum obtained from an individual who has been immunized with a fHbp, to inhibit binding of human factor H (1H) to fHbp, wherein inhibition of binding of fH to fHbp by the antibody at a level that is at least about 25% higher than the level of inhibition of fH to fHbp by a control antibody that inhibits fH binding to fHbp but that does not generate a bactericidal response indicates that the fHbp is likely to elicit a bactericidal response to at least one Neisseria meningitidis strain.
A method of determining the likelihood that a non-naturally occurring factor H binding protein (fHbp) that has lower affinity for human factor H (fH) than fHbp ID 1 will elicit bactericidal antibodies in an individual to at least one Neisseria meningitidis strain, the method comprising:
- determining the ability of an antibody elicited in a test non-human animal to the non-naturally occurring fHbp to inhibit binding of fH to fHbp,
- wherein inhibition of binding of fH to fHbp by the antibody elicited to the non-naturally occurring fHbp at a level that is at least about 25% higher than the level of inhibition of fH to fHbp by an antibody elicited in the test non-human animal to fHbp ID 1 indicates that the non-naturally occurring fHbp is likely to elicit a bactericidal response to at least one Neisseria meningitidis strain.
Dependencies are inferred from the claim text.