Monoclonal antibody and vaccine targeting filamentous bacteriophage

Abstract

Described here is a method for reducing or preventing Pseudomonas aeruginosa biofilm formation in a human subject in need thereof, comprising administering to the human subject a first composition comprising (a) an antigen-binding polypeptide that binds Pf-family bacteriophage, or (b) a vaccine against Pf-family bacteriophage. Also described is an antigen-binding polypeptide that binds specifically to a CoaB protein of Pf-family bacteriophage or fragment thereof.

What is claimed is: 
     
         1 . A method for reducing or preventing  Pseudomonas aeruginosa  biofilm formation in a human subject in need thereof, comprising administering to the human subject a first composition comprising (a) an antigen-binding polypeptide that binds Pf-family bacteriophage, or (b) a vaccine against Pf-family bacteriophage. 
     
     
         2 . The method of  claim 1 , wherein the first composition comprises the antigen-binding polypeptide. 
     
     
         3 . The method of  claim 2 , wherein the antigen-binding polypeptide binds specifically to a CoaB protein of Pf-family bacteriophage or fragment thereof. 
     
     
         4 . The method of  claim 2 , wherein the antigen-binding polypeptide is IgG or IgM. 
     
     
         5 . The method of  claim 2 , wherein the first composition further comprises an antibiotic, or wherein the method further comprises administering a second composition comprising an antibiotic to the human subject. 
     
     
         6 . The method of  claim 5 , wherein the human subject is infected with a  Pseudomonas aeruginosa  strain resistant to one or more antibiotics. 
     
     
         7 . The method of  claim 1 , wherein the first composition comprises the vaccine against Pf-family bacteriophage. 
     
     
         8 . The method of  claim 7 , wherein the vaccine comprises an immunogenic fragment of CoaB protein of Pf-family bacteriophage. 
     
     
         9 . The method of  claim 8 , wherein the CoaB protein or fragment thereof comprises the amino acid sequence of GVIDTSAVESAITDGQGDM (SEQ ID NO: 1). 
     
     
         10 . The method of  claim 1 , wherein the human subject is suffering from cystic fibrosis, burns, chronic would, chronic rhinosinusitis, ventilator-associated pneumonia, catheter-associated urinary tract infections, septic shock, and/or gastrointestinal infections. 
     
     
         11 . An antigen-binding polypeptide that binds specifically to a CoaB protein of Pf-family bacteriophage or fragment thereof. 
     
     
         12 . The antigen-binding polypeptide of  claim 11 , wherein the antigen-binding polypeptide specifically binds to an antigenic fragment of the CoaB protein comprising the amino acid sequence of GVIDTSAVESAITDGQGDM (SEQ ID NO: 1). 
     
     
         13 . The antigen-binding polypeptide of  claim 11 , wherein the antigen-binding polypeptide comprises:
 (a) a heavy chain variable region comprising (1) the CDR-H1 comprising, consisting essentially of or consisting of the amino acid sequence of GFTFSSYV (SEQ ID NO: 6); (2) the CDR-H2 comprising, consisting essentially of or consisting of the amino acid sequence of ISSGGST (SEQ ID NO: 7); and (3) the CDR-H3 comprising, consisting essentially of or consisting of the amino acid sequence of LRGQDYGAAY (SEQ ID NO: 8),   a heavy chain variable region comprising (1) the CDR-H1 comprising, consisting essentially of or consisting of the amino acid sequence of GYSFTSYW (SEQ ID NO: 16); (2) the CDR-H2 comprising, consisting essentially of or consisting of the amino acid sequence of IYPGNSDT (SEQ ID NO: 17); and (3) the CDR-H3 comprising, consisting essentially of or consisting of the amino acid sequence of TRSQFYSGSSEDAMDY (SEQ ID NO: 18), or   a heavy chain variable region comprising (1) the CDR-H1 comprising, consisting essentially of or consisting of the amino acid sequence of GYTFTNYG (SEQ ID NO: 26); (2) the CDR-H2 comprising, consisting essentially of or consisting of the amino acid sequence of INTNTGEP (SEQ ID NO: 27); and (3) the CDR-H3 comprising, consisting essentially of or consisting of the amino acid sequence of ARKDYRYWFAY (SEQ ID NO: 28); and   (b) a light chain variable region comprising (1) the CDR-L1 comprising, consisting essentially of or consisting of the amino acid sequence of QSLLDSDGKTY (SEQ ID NO: 9); (2) the CDR-L2 comprising, consisting essentially of or consisting of the amino acid sequence of LVS (SEQ ID NO: 10); and (3) the CDR-L3 comprising, consisting essentially of or consisting of the amino acid sequence of WQGTHFPQT (SEQ ID NO: 11),   a light chain variable region comprising (1) the CDR-L1 comprising, consisting essentially of or consisting of the amino acid sequence of QSIVHSNGNTY (SEQ ID NO: 19); (2) the CDR-L2 comprising, consisting essentially of or consisting of the amino acid sequence of KVS (SEQ ID NO: 20); and (3) the CDR-L3 comprising, consisting essentially of or consisting of the amino acid sequence of FQGSHVPWT (SEQ ID NO: 21), or   a light chain variable region comprising (1) the CDR-L1 comprising, consisting essentially of or consisting of the amino acid sequence of QSIVHSNGNTY (SEQ ID NO: 29); (2) the CDR-L2 comprising, consisting essentially of or consisting of the amino acid sequence of KVS (SEQ ID NO: 30); and (3) the CDR-L3 comprising, consisting essentially of or consisting of the amino acid sequence of FQGSHVPFT (SEQ ID NO: 31).   
     
     
         14 . The antigen-binding polypeptide of  claim 11 , wherein the antigen-binding polypeptide is a monoclonal antibody, a chimeric antibody, a humanized antibody, a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, or an scFv molecule. 
     
     
         15 . A pharmaceutical composition comprising (a) the antigen-binding polypeptide of  claim 11  or a fusion molecule comprising the antigen-binding polypeptide of  claim 11 , and (b) a pharmaceutically acceptable carrier. 
     
     
         16 . A polynucleotide encoding the antigen-binding polypeptide of  claim 11 . 
     
     
         17 . An expression cassette comprising a promoter operably linked to the polynucleotide of  claim 16 . 
     
     
         18 . A vector comprising the expression cassette of  claim 17 . 
     
     
         19 . A transformed cell comprising the expression cassette of  claim 17 . 
     
     
         20 . A vaccine against Pf-family bacteriophage, comprising (a) an immunogenic fragment of CoaB protein of Pf-family bacteriophage comprising the amino acid sequence of GVIDTSAVESAITDGQGDM (SEQ ID NO: 1), and (b) a pharmaceutically acceptable carrier.