Chaperone and adhesin proteins; vaccines, diagnostics and method for treating infections

Abstract

The present invention provides bacterial immunogenic agents for administration to humans and non-human animals to stimulate an immune response. It particularly relates to the vaccination of mammalian species with heteropolymeric protein complexes as a mechanism for stimulating production of antibodies that protect the vaccine recipient against infection by pathogenic bacterial species. In another aspect the invention provides antibodies against such proteins and protein complexes that may be used as diagnostics and/or as protective/treatment agents for pathogenic bacterial species. A novel vector for expressing the FimC-H complex at optimal levels is also disclosed.

What is claimed is:  
     
         1 . A vaccine against bacterial infections comprising a complex of a bacterial chaperone protein with either an adhesin protein or an immunogenic fragment of said adhesin protein.  
     
     
         2 . A vaccine according to  claim 1 , wherein said vaccine is for urinary tract infections.  
     
     
         3 . A vaccine according to  claim 2 , wherein said vaccine is for bladder infections.  
     
     
         4 . A vaccine according to  claim 3 , wherein said vaccine is for bladder infections caused by  E. coli.    
     
     
         5 . A vaccine according to  claim 1 , wherein said immunogenic fragment of said adhesin protein is a mannose-binding fragment.  
     
     
         6 . A vaccine according to  claim 1  wherein said adhesin protein is FimH, and said fragment is a mannose-binding fragment of FimH.  
     
     
         7 . A vaccine according to  claim 4 , wherein said chaperone protein is FimC.  
     
     
         8 . A vaccine against bacterial infections comprising the bacterial adhesin protein FimH or a mannose-binding fragment of FimH.  
     
     
         9 . An antibody raised against a complex of a bacterial chaperone protein with either an adhesin protein or an immunogenic fragment of said adhesin protein.  
     
     
         10 . An antibody according to  claim 9 , wherein said antibody is an antibody that will detect urinary tract infections.  
     
     
         11 . An antibody according to  claim 9 , wherein said antibody is effective for the prevention and/or treatment of urinary tract infections.  
     
     
         12 . An antibody according to  claim 9 , wherein said antibody is effective for the prevention and/or treatment of urinary tract infections caused by  E. coli  bacteria.  
     
     
         13 . An antibody according to  claim 9 , wherein said immunogenic fragment of said adhesin protein is a mannose-binding fragment.  
     
     
         14 . A antibody according to  claim 9  wherein said adhesin protein is FimH, and said fragment is a mannose-binding fragment of FimH.  
     
     
         15 . An antibody according to  claim 7 , wherein said chaperone protein is FimC.  
     
     
         16 . An antibody raised against either the bacterial adhesin protein FimH or an immunogenic mannose-binding fragment of FimH.  
     
     
         17 . A method for preventing and or treating UTIs in a host comprising immunizing said host with a member selected from the group consisting of: 
 (a) a vaccine according to  claim 1 , and    (b) at least one antibody raised against a complex of a bacterial chaperone protein with either an adhesin protein or an immunogenic mannose-binding fragment of said adhesin protein.    
     
     
         18 . A method for preventing and or treating enterobacterial infections in a host comprising immunizing said host with a member selected from the group consisting of: 
 (a) a vaccine according to  claim 7 , and    (b) at least one antibody raised against a complex of a FimC with either FimH or an immunogenic mannose-binding fragment of FimH.    
     
     
         19 . The method according to  claim 18  wherein the enterobacterial infection is a urinary tract infection (or UTI).  
     
     
         20 . A method for preventing and or treating an enterobacterial infection in a host comprising immunizing said host with a member selected from the group consisting of: 
 (a) a vaccine according to  claim 8 , and    (b) at least one antibody raised against FimH or an immunogenic mannose-binding fragment of FimH.    
     
     
         21 . The method according to  claim 20  wherein the enterobacterial infection is a urinary tract infection (or UTI).  
     
     
         22 . A method according to  claim 21  wherein the UTI is caused by  E. coli  bacteria.  
     
     
         23 . A method for expressing a protein complex in a bacterial cell comprising inserting into said cell a vector containing the protein complex genes, wherein each said gene has a lac promoter attached in 5′ orientation with respect to each said gene.  
     
     
         24 . The method of  claim 23  wherein the protein complex is an adhesin/chaperone complex.  
     
     
         25 . The method of  claim 23  wherein said bacterial cell is an  Escherichia coli  cell.  
     
     
         26 . The method according to  claim 23  wherein the vector is a modified pUC19 vector.