Chimeric Factor H Binding Proteins (fHBP) and Methods of Use

Abstract

Chimeric fHbps that can elicit antibodies that are bactericidal for different fHbp variant strains of N. meningitidis , and methods of use, are provided.

What is claimed is: 
     
         1 . A non-naturally occurring fHbp of  claim 1 , comprising, from N-terminus to C-terminus:
     V   A - I   3 - V   B - I   4 - V   C - I   5 - V   D - I   6 - V   E ,   
       wherein the combination of alleles for each of V A , V B , V C , V D , and V E  variable segments is not found in nature. 
     
     
         2 . The non-naturally occurring fHbp of  claim 1 , wherein each of said variable segments is an α progenitor sequence. 
     
     
         3 . The non-naturally occurring fHbp of  claim 1 , wherein each of said variable segments is a β progenitor sequence. 
     
     
         4 . The non-naturally occurring fHbp of  claim 1 ,
 wherein at least one of V A , V B , V C , V D , and V E  is of an α progenitor fHbp amino acid sequence and at least one of V A , V B , V C , V D , and V E  is of an β progenitor fHbp amino acid sequence.   
     
     
         5 . The non-naturally occurring fHbp of  claim 4 , wherein said non-naturally occurring fHbp is not of a modular group Type as set forth in  FIG. 8 . 
     
     
         6 . The non-naturally occurring fHbp of  claim 1 , where said non-naturally occurring fHbp comprises, from N-terminus to C-terminus:
     I   1 - Nte - I   2 - V   A - I   3 - V   B - I   4 - V   C - I   5 - V   D - I   6 - V   E - I   7 .   
     
     
         7 . The non-naturally occurring fHbp of  claim 1 , where said non-naturally occurring fHbp comprises, from N-terminus to C-terminus:
     V   A α- I   3 - V   B α- I   4 - V   C α- I   5 - V   D β- I   6 - V   E α or
       V   A α- I   3 - V   B α- I   4 - V   C α- I   5 - V   D β- I   6 - V   E β.
   
     
     
         8 . The non-naturally occurring fHbp of  claim 1 , wherein said fHbp comprises an epitope that is bound by a monoclonal antibody set forth in Table 1. 
     
     
         9 . A method of eliciting an antibody response in a mammal, the method comprising administering to a mammal a composition comprising a first non-naturally occurring fHbp according to  claim 1 . 
     
     
         10 . The method of  claim 9 , wherein the mammal is a human. 
     
     
         11 . The method of  claim 9 , wherein said administering provides for production of antibodies that bind to two or more types of fHbp. 
     
     
         12 . The method of  claim 9 , wherein said non-naturally occurring fHbp is in a preparation comprising outer membrane vesicles (OMVs), microvesicles (MVs), or a mixture of OMVs and MVs. 
     
     
         13 . The method of  claim 12 , wherein said vesicles are prepared from two or more strains of  N. meningitidis , each of which is genetically different from the other. 
     
     
         14 . The method of  claim 9 , wherein said administering comprises administering a second fHbp, wherein said second fHbp is different from said first non-naturally occurring fHbp. 
     
     
         15 . An immunogenic composition comprising a first non-naturally occurring fHbp according to  claim 1 , and a pharmaceutically acceptable excipient. 
     
     
         16 . The immunogenic composition of  claim 15 , further comprising a second fHbp, wherein said second fHbp is different from said first non-naturally occurring fHbp. 
     
     
         17 . The immunogenic composition of  claim 15 , wherein said non-naturally occurring fHbp is in a vesicle preparation, wherein vesicles are prepared from a  Neisseria  bacterium. 
     
     
         18 . The immunogenic composition of  claim 17 , wherein said  Neisseria  bacterium is genetically modified to disrupt production of an endogenous fHbp polypeptide. 
     
     
         19 . The immunogenic composition of  claim 15 , wherein said non-naturally occurring fHbp is produced by a  Neisseria  bacterium that is genetically modified to produce said fHbp. 
     
     
         20 . The immunogenic composition of  claim 18 , wherein said vesicle preparation is from the same  Neisseria meningitidis  strain as the strain producing said non-naturally occurring fHbp. 
     
     
         21 . The immunogenic composition of  claim 18 , wherein said  Neisseria  bacterium is deficient in capsular polysaccharide synthesis. 
     
     
         22 . A nucleic acid encoding the non-naturally occurring fHbp of  claim 1 . 
     
     
         23 . A host cell containing the nucleic acid of  claim 22 .