Poly-n-acetyl glucosamine (PNAG/dPNAG)-binding peptides and methods of use thereof
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 method of treating a subject having or at risk of developing an infection by a bacterial strain expressing poly-N-acetyl glucosamine (PNAG) comprising
administering to a subject in need of such treatment an effective amount of an antibody or antibody fragment comprising the amino acid sequences of SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9.
2. The method of claim 1 , wherein the antibody or antibody fragment comprises the amino acid sequence of SEQ ID NO: 1.
3. The method of claim 1 , wherein the antibody or antibody fragment further comprises the amino acid sequences of SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12.
4. The method of claim 1 , wherein the antibody or antibody fragment further comprises the amino acid sequence of SEQ ID NO: 2.
5. The method of claim 1 , wherein the antibody or antibody fragment comprises an IgG1 constant region.
6. The method of claim 1 , wherein the antibody or antibody fragment is a monoclonal antibody.
7. The method of claim 6 , wherein the monoclonal antibody is produced from a deposited hybridoma having Accession No. PTA-5931 (F598).
8. The method of claim 1 , wherein the antibody or antibody fragment is an antibody fragment selected from the group consisting of an F(ab′)2 fragment, an Fd fragment and an Fab fragment.
9. The method of claim 1 , wherein the antibody or antibody fragment is produced from a deposited hybridoma having Accession No. PTA-5931 (F598).
10. The method of claim 1 , wherein the bacterial strain expressing PNAG is selected from the group consisting of E. coli, Yersinia pestis ( Y. pestis ), E entercolitica, Xanthomonas axonopodis ( X. axonopodis ), Pseudomonas fluorescens ( P. fluorescens ), Actinobacillus actinomycetemcomitans ( A. actinomycetemcomitans ), A. pleuropneumoniae, Ralstonia solanacearum ( R. solanacearum ), Bordetella pertussis ( B. pertussis ), B. parapertussis and B. bronchiseptica.
11. The method of claim 1 , wherein the subject has an infection by a bacterial strain expressing PNAG.
12. The method of claim 1 , wherein the subject is at risk of developing an infection by a bacterial strain expressing PNAG.
13. A method of treating a subject having or at risk of developing an infection by a bacterial strain expressing poly-N-acetyl glucosamine (PNAG) comprising
administering to a subject in need of such treatment an effective amount of an antibody or antibody fragment that selectively binds to poly-N-acetyl glucosamine (PNAG) and deacetylated PNAG and comprises the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 2 or a functionally equivalent peptide variant thereof, wherein the variant comprises an amino acid sequence having at least 90% amino acid identity to SEQ ID NO: 1 and at least 90% amino acid identity to SEQ ID NO: 2.
14. The method of claim 13 , wherein the variant comprises an amino acid sequence having at least 95% amino acid identity to SEQ ID NO: 1 and at least 95% amino acid identity to SEQ ID NO: 2.
15. The method of claim 13 , wherein the variant comprises an amino acid sequence having 5, 4, 3, 2 or 1 amino acid difference to SEQ ID NO: 1 and having 5, 4, 3, 2 or 1 amino acid difference to SEQ ID NO: 2.
16. The method of claim 13 , wherein the functionally equivalent peptide variant is derived from SEQ ID NO: 1 by means of phage display antibody selection.
17. The method of claim 13 , wherein the functionally equivalent peptide variant is derived from SEQ ID NO: 2 by means of phage display antibody selection.
18. The method of claim 15 , wherein the functionally equivalent peptide variant is derived from SEQ ID NO: 1 by means of phage display antibody selection.
19. The method of claim 15 , wherein the functionally equivalent peptide variant is derived from SEQ ID NO: 2 by means of phage display antibody selection.