Monoclonal antibody and vaccine targeting filamentous bacteriophage
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.
1 . A method of inhibiting Pseudomonas aeruginosa biofilm formation in an animal or a human subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of one or more antibodies targeting a CoaB protein of Pf4 bacteriophage or an antigenic fragment thereof, wherein the one or more antibodies comprises:
a heavy chain variable region comprising: (1) the CDR-H1 comprising the amino acid sequence of GFTFSSYV (SEQ ID NO: 6); (2) the CDR-H2 comprising the amino acid sequence of ISSGGST (SEQ ID NO: 7); and (3) the CDR-H3 comprising the amino acid sequence of LRGQDYGAAY (SEQ ID NO: 8) and
a light chain variable region comprising: (1) the CDR-L1 comprising the amino acid sequence of QSLLDSDGKTY (SEQ ID NO: 9); (2) the CDR-L2 comprising the amino acid sequence of LVS (SEQ ID NO: 10); and (3) the CDR-L3 comprising the amino acid sequence of WQGTHFPQT (SEQ ID NO: 11);
a heavy chain variable region comprising: (1) the CDR-H1 comprising the amino acid sequence of GYSFTSYW (SEQ ID NO: 16); (2) the CDR-H2 comprising the amino acid sequence of IYPGNSDT (SEQ ID NO: 17); and (3) the CDR-H3 comprising the amino acid sequence of TRSQFYSGSSEDAMDY (SEQ ID NO: 18) and
a light chain variable region comprising: (1) the CDR-L1 comprising the amino acid sequence of QSIVHSNGNTY (SEQ ID NO: 19); (2) the CDR-L2 comprising the amino acid sequence of KVS (SEQ ID NO: 20); and (3) the CDR-L3 comprising the amino acid sequence of FQGSHVPWT (SEQ ID NO: 21);
a heavy chain variable region comprising: (1) the CDR-H1 comprising the amino acid sequence of GYTFTNYG (SEQ ID NO: 26); (2) the CDR-H2 comprising the amino acid sequence of INTNTGEP (SEQ ID NO: 27); and (3) the CDR-H3 comprising the amino acid sequence ofARKDYRYWFAY (SEQ ID NO: 28) and
a light chain variable region comprising: (1) the CDR-L1 comprising the amino acid sequence of QSIVHSNGNTY (SEQ ID NO: 29); (2) the CDR-L2 comprising the amino acid sequence of KVS (SEQ ID NO: 30); and (3) the CDR-L3 comprising the amino acid sequence of FQGSHVPFT (SEQ ID NO: 31).
2 . The method of claim 1 , wherein the animal or the human subject is suffering from cystic fibrosis, burns, chronic wound, chronic rhinosinusitis, ventilator-associated pneumonia, catheter-associated urinary tract infections, septic shock, or gastrointestinal infections caused by Pseudomonas aeruginosa.