Poly-n-acetyl glucosamine (pnag/dpnag)-binding peptides and methods of use thereof

Abstract

The present invention relates to peptides, particularly human monoclonal antibodies, that bind specifically to poly-N-acetyl glucosamine (PNAG), such as Staphylococcal PNAG, in acetylated, partially acetylated and/or fully deacetylated form. The invention further provides methods for using these peptides in the diagnosis, prophylaxis and therapy of infections by bacteria that express PNAG such as but not limited to Staphylococci and E. coli . Some antibodies of the invention enhance opsonophagocytic killing and in vivo protection against bacteria that express PNAG such as but not limited to Staphylococci and E. coli . Compositions of these peptides, including pharmaceutical compositions, are also provided, as are functionally equivalent variants of such peptides.

1 . A composition comprising:
 an isolated nucleic acid molecule having the nucleotide sequences of SEQ ID NO: 37, SEQ ID NO: 38, and SEQ ID NO: 39; and   an isolated nucleic acid molecule having the nucleotide sequences of SEQ ID NO: 40, SEQ ID NO: 41 and SEQ ID NO: 42.   
     
     
         2 . The composition of  claim 1 , wherein the nucleotide sequences of SEQ ID NO: 37, SEQ ID NO: 38 and SEQ ID NO: 39 encode a heavy chain variable region of Staphylococcal poly-N-acetyl glucosamine/dPNAG-binding antibody (PNAG/dPNAG-binding antibody) and the nucleotide sequences of SEQ ID NO: 40, SEQ ID NO: 41 and SEQ ID NO: 42 encode a light chain variable region of PNAG/dPNAG-binding antibody, the heavy chain variable region comprising a CDR1 having an amino acid sequence of SEQ ID NO: 13, a CDR2 having an amino acid sequence of SEQ ID NO: 14, and a CDR3 having an amino acid sequence of SEQ ID NO: 15, and the light chain variable region comprising a CDR1 having an amino acid sequence of SEQ ID NO: 16, a CDR2 having an amino acid sequence of SEQ ID NO: 17, and a CDR3 having an amino acid sequence of SEQ ID NO: 18. 
     
     
         3 . The composition of  claim 1  wherein the nucleic acid molecule is derived from a hybridoma having Accession No. PTA-5932. 
     
     
         4 . The composition of  claim 2  wherein the nucleic acid molecule is derived from a hybridoma having Accession No. PTA-5932. 
     
     
         5 . An expression vector comprising the isolated nucleic acid molecules of  claim 1 , operably linked to a promoter. 
     
     
         6 . A host cell transformed or transfected with the expression vector of  claim 5 . 
     
     
         7 - 8 . (canceled) 
     
     
         9 . An expression vector comprising the isolated nucleic acid molecule having the nucleotide sequences of SEQ ID NO: 40, SEQ ID NO: 41 and SEQ ID NO: 42, operably linked to a promoter. 
     
     
         10 . A host cell transformed or transfected with the expression vector of  claim 9 . 
     
     
         11 - 13 . (canceled) 
     
     
         14 . A composition, comprising
 an isolated peptide that selectively binds to Staphylococcal poly-N-acetyl glucosamine (PNAG/dPNAG) and comprises an amino acid sequence of a Staphylococcal PNAG/dPNAG-binding CDR, or functionally equivalent variant thereof.