Specificity exchangers that redirect antibodies to a pathogen

Abstract

Specificity exchangers and methods of making and using specificity exchangers are disclosed. Specificity exchangers are useful for preventing and treating human diseases including cancer and those resulting from pathogens such as bacteria, yeast, parasites, fungus, viruses, and the like. More specifically, specificity exchangers can redirect existing antibodies in a subject to pathogens and cancer cells.

1 . A ligand/receptor specificity exchanger comprising a specificity domain that comprises a ligand for a bacterial adhesion receptor joined to an antigenic domain, wherein said antigenic domain is an oligosaccharide.  
     
     
         2 . The ligand/receptor specificity exchanger of  claim 1 , wherein said ligand for a bacterial adhesion receptor is fibrinogen or a fragment thereof.  
     
     
         3 . The ligand/receptor specificity exchanger of  claim 1 , wherein the length of said specificity domain is between 3-200 amino acids.  
     
     
         4 . The ligand/receptor specificity exchanger of  claim 1 , wherein the length of said specificity domain is between 5-100 amino acids.  
     
     
         5 . The ligand/receptor specificity exchanger of  claim 1 , wherein the length of said specificity domain is between 8-50 amino acids.  
     
     
         6 . The ligand/receptor specificity exchanger of  claim 1 , wherein the length of said specificity domain is between 10-25 amino acids.  
     
     
         7 . The ligand/receptor specificity exchanger of  claim 1 , wherein said bacterial adhesion receptor is selected from the group consisting of extracellular fibrinogen binding protein (Efb), collagen binding protein, vitronectin binding protein, laminin binding protein, plasminogen binding protein, thrombospondin binding protein, clumping factor A (ClfA), clumping factor B (ClfB), fibronectin binding protein, coagulase, and extracellular adherence protein.  
     
     
         8 . The ligand/receptor specificity exchanger of  claim 1 , wherein said specificity exchanger comprises a specificity domain selected from the group consisting of SEQ. ID. No. 1, SEQ. ID. No. 2, SEQ. ID. No. 3, SEQ. ID. No. 4, SEQ. ID. No. 5, SEQ. ID. No. 6, SEQ. ID. No. 7, SEQ. ID. No. 8, SEQ. ID. No. 9, SEQ. ID. No. 10, SEQ. ID. No. 11, SEQ. ID. No. 12, SEQ. ID. No. 13, SEQ. ID. No. 14, SEQ. ID. No. 15, SEQ. ID. No. 16, SEQ. ID. No. 17, SEQ. ID. No. 18, SEQ. ID. No. 19, SEQ. ID. No. 20, SEQ. ID. No. 21, SEQ. ID. No. 22, SEQ. ID. No. 23, SEQ. ID. No. 24, SEQ. ID. No. 25, SEQ. ID. No. 26, SEQ. ID. No. 27, SEQ. ID. No. 28, SEQ. ID. No. 29, SEQ. ID. No. 30, SEQ. ID. No. 31, SEQ. ID. No. 32, SEQ. ID. No. 33, SEQ. ID. No. 34, SEQ. ID. No. 35, SEQ. ID. No. 36, SEQ. ID. No. 37, SEQ. ID. No. 38, SEQ. ID. No. 39, SEQ. ID. No. 40, SEQ. ID. No. 41, SEQ. ID. No. 42, SEQ. ID. No. 43, SEQ. ID. No. 44, SEQ. ID. No. 45, SEQ. ID. No. 46, and SEQ. ID. No. 47.  
     
     
         9 . A method of redirecting an antibody present in human serum to a bacterial adhesion receptor comprising: 
 providing a specificity exchanger that comprises a specificity domain, which comprises a ligand for a bacterial adhesion receptor, joined to an antigenic domain, which comprises an epitope of a pathogen;    contacting said specificity exchanger with a bacterial adhesion receptor;    contacting said specificity exchanger with an antibody that is present in human serum, which is specific for said epitope; and    detecting a redirection of said antibody to said bacterial adhesion receptor.    
     
     
         10 . The method of  claim 9 , wherein said antigenic domain is an oligosaccharide.  
     
     
         11 . The method of  claim 9 , wherein said ligand for a bacterial adhesion receptor is fibrinogen or a fragment thereof.  
     
     
         12 . The method of  claim 9 , wherein the length of said specificity domain is between 3-200 amino acids.  
     
     
         13 . The method of  claim 9 , wherein the length of said specificity domain is between 5-100 amino acids.  
     
     
         14 . The method of  claim 9 , wherein the length of said specificity domain is between 8-50 amino acids.  
     
     
         15 . The method of  claim 9 , wherein the length of said specificity domain is between 10-25 amino acids.  
     
     
         16 . The method of  claim 9 , wherein said bacterial adhesion receptor is selected from the group consisting of extracellular fibrinogen binding protein (Efb), collagen binding protein, vitronectin binding protein, laminin binding protein, plasminogen binding protein, thrombospondin binding protein, clumping factor A (ClfA), clumping factor B (ClfB), fibronectin binding protein, coagulase, and extracellular adherence protein.  
     
     
         17 . The method of  claim 9 , wherein said specificity exchanger comprises a specificity domain selected from the group consisting of SEQ. ID. No. 1, SEQ. ID. No. 2, SEQ. ID. No. 3, SEQ. ID. No. 4, SEQ. ID. No. 5, SEQ. ID. No. 6, SEQ. ID. No. 7, SEQ. ID. No. 8, SEQ. ID. No. 9, SEQ. ID. No. 10, SEQ. ID. No. 11, SEQ. ID. No. 12, SEQ. ID. No. 13, SEQ. ID. No. 14, SEQ. ID. No. 15, SEQ. ID. No. 16, SEQ. ID. No. 17, SEQ. ID. No. 18, SEQ. ID. No. 19, SEQ. ID. No. 20, SEQ. ID. No. 21, SEQ. ID. No. 22, SEQ. ID. No. 23, SEQ. ID. No. 24, SEQ. ID. No. 25, SEQ. ID. No. 26, SEQ. ID. No. 27, SEQ. ID. No. 28, SEQ. ID. No. 29, SEQ. ID. No. 30, SEQ. ID. No. 31, SEQ. ID. No. 32, SEQ. ID. No. 33, SEQ. ID. No. 34, SEQ. ID. No. 35, SEQ. ID. No. 36, SEQ. ID. No. 37, SEQ. ID. No. 38, SEQ. ID. No. 39, SEQ. ID. No. 40, SEQ. ID. No. 41, SEQ. ID. No. 42, SEQ. ID. No. 43, SEQ. ID. No. 44, SEQ. ID. No. 45, SEQ. ID. No. 46, and SEQ. ID. No. 47.  
     
     
         18 . A method of redirecting an antibody present in human serum to a bacterial adhesion receptor comprising: 
 providing a specificity exchanger that comprises a specificity domain, which comprises a ligand for a bacterial adhesion receptor, joined to an antigenic domain that comprises a means to bind an antibody present in human serum;    contacting said specificity exchanger with a bacterial adhesion receptor;    contacting said specificity exchanger with an antibody that is present in human serum, which is specific for said antigenic domain; and    detecting a redirection of said antibody to said bacterial adhesion receptor.    
     
     
         19 . The method of  claim 18 , wherein said specificity exchanger comprises an oligosaccharide.  
     
     
         20 . The method of  claim 18 , wherein said ligand for a bacterial adhesion receptor is fibrinogen or a fragment thereof.  
     
     
         21 . The method of  claim 18 , wherein the length of said specificity domain is between 3-200 amino acids.  
     
     
         22 . The method of  claim 18 , wherein the length of said specificity domain is between 5-100 amino acids.  
     
     
         23 . The method of  claim 18 , wherein the length of said specificity domain is between 8-50 amino acids.  
     
     
         24 . The method of  claim 18 , wherein the length of said specificity domain is between 10-25 amino acids.  
     
     
         25 . The method of  claim 18 , wherein said bacterial adhesion receptor is selected from the group consisting of extracellular fibrinogen binding protein (Efb), collagen binding protein, vitronectin binding protein, laminin binding protein, plasminogen binding protein, thrombospondin binding protein, clumping factor A (ClfA), clumping factor B (ClfB), fibronectin binding protein, coagulase, and extracellular adherence protein.  
     
     
         26 . The method of  claim 18 , wherein said specificity domain is selected from the group consisting of SEQ. ID. No. 1, SEQ. ID. No. 2, SEQ. ID. No. 3, SEQ. ID. No. 4, SEQ. ID. No. 5, SEQ. ID. No. 6, SEQ. ID. No. 7, SEQ. ID. No. 8, SEQ. ID. No. 9, SEQ. ID. No. 10, SEQ. ID. No. 11, SEQ. ID. No. 12, SEQ. ID. No. 13, SEQ. ID. No. 14, SEQ. ID. No. 15, SEQ. ID. No. 16, SEQ. ID. No. 17, SEQ. ID. No. 18, SEQ. ID. No. 19, SEQ. ID. No. 20, SEQ. ID. No. 21, SEQ. ID. No. 22, SEQ. ID. No. 23, SEQ. ID. No. 24, SEQ. ID. No. 25, SEQ. ID. No. 26, SEQ. ID. No. 27, SEQ. ID. No. 28, SEQ. ID. No. 29, SEQ. ID. No. 30, SEQ. ID. No. 31, SEQ. ID. No. 32, SEQ. ID. No. 33, SEQ. ID. No. 34, SEQ. ID. No. 35, SEQ. ID. No. 36, SEQ. ID. No. 37, SEQ. ID. No. 38, SEQ. ID. No. 39, SEQ. ID. No. 40, SEQ. ID. No. 41, SEQ. ID. No. 42, SEQ. ID. No. 43, SEQ. ID. No. 44, SEQ. ID. No. 45, SEQ. ID. No. 46, and SEQ. ID. No. 47.