The present invention relates to peptides, particularly human monoclonal antibodies, that bind specifically to P. aeruginosa mucoid exopolysaccharide. The invention further provides methods for using these peptides in the diagnosis, prophylaxis and therapy of P. aeruginosa infection and related disorders (e.g., cystic fibrosis). Some antibodies of the invention enhance opsonophagocytic killing of multiple mucoid strains of P. aeruginosa . Compositions of these peptides, including pharmaceutical compositions, are also provided, as are functionally equivalent variants of such peptides.
1. A composition, comprising an isolated peptide that selectively binds to P. aeruginosa mucoid exopolysaccharide and comprises an amino acid sequence selected from the group consisting of SEQ ID NO:5 and SEQ ID NO:8 or a variant having at least 95% identity to SEQ ID NO:5 or SEQ ID NO:8.
2. The composition of claim 1 , wherein the isolated peptide comprises amino acid sequence SEQ ID NO:5.
3. The composition of claim 1 , wherein the isolated peptide comprises amino acid sequence SEQ ID NO:8.
4. The composition of claim 1 , wherein the isolated peptide is an isolated antibody or antibody fragment.
5. The composition of claim 4 , wherein the isolated antibody or antibody fragment is an intact soluble monoclonal antibody.
6. The composition of claim 4 , wherein the isolated antibody or antibody fragment is an isolated monoclonal antibody fragment selected from the group consisting of an F(ab′) 2 fragment, an Fd fragment, and an Fab fragment.
7. The composition of claim 4 , wherein the isolated antibody or antibody fragment enhances opsonophagocytosis of P. aeruginosa.
8. The composition of claim 4 , wherein the isolated antibody or antibody fragment comprises
an amino acid sequence selected from the group consisting of SEQ ID NO:5 and SEQ ID NO:8, and
an amino acid sequence selected from the group consisting of SEQ ID NO:6 and SEQ ID NO:7.
9. The composition of claim 4 , wherein the isolated antibody or antibody fragment comprises an amino acid sequence of SEQ ID NO:5 and an amino acid sequence of SEQ ID NO:6.
10. The composition of claim 4 , wherein the isolated antibody or antibody fragment comprises an amino acid sequence of SEQ ID NO:5 and an amino acid sequence of SEQ ID NO:7.
11. The composition of claim 4 , wherein the isolated antibody or antibody fragment comprises an amino acid sequence of SEQ ID NO:8 and an amino acid sequence of SEQ ID NO:6.
12. The composition of claim 4 , wherein the isolated antibody or antibody fragment comprises an amino acid sequence of SEQ ID NO:8 and an amino acid sequence of SEQ ID NO:7.
13. The composition of claim 1 , wherein the isolated peptide is conjugated to a detectable label.
14. The composition of claim 1 , wherein the composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier.
15. The composition of claim 4 , wherein the isolated antibody or antibody fragment is present in an effective amount for inhibiting a P. aeruginosa infection.
16. The composition of claim 4 , wherein the isolated antibody or antibody fragment is present in an effective amount for inhibiting a disorder associated with the presence of P. aeruginosa infection.
17. The composition of claim 14 , wherein the isolated peptide is present in an effective amount for detecting P. aeruginosa in a sample in or from a subject.
18. The composition of claim 4 , wherein the isolated antibody or antibody fragment is a human antibody or antibody fragment.
19. A method for detecting P. aeruginosa in a subject comprising
determining a test level of binding of the isolated peptide of claim 1 to a sample in or from a subject, and
comparing the test level of binding to a control,
wherein a test level of binding that is greater than the control is indicative of the presence of P. aeruginosa in the sample.
20. A method for treating a subject having, or at risk of developing, a P. aeruginosa infection comprising
administering to a subject in need of such treatment the isolated peptide of claim 1 in an amount effective to inhibit a P. aeruginosa infection.
21. The composition of claim 4 , wherein the isolated antibody or antibody fragment is an IgG, IgA or IgM isotype.
22. The composition of claim 4 , wherein the isolated antibody fragment is an Fv.
23. A composition, comprising an isolated peptide that selectively binds to P. aeruginosa mucoid exopolysaceharide and comprises an amino acid sequence selected from the group consisting of SEQ ID NO:6 and SEQ ID NO:7 or a variant having at least 95% identity to SEQ ID NO:6 or SEQ ID NO:7.
24. The composition of claim 23 , wherein the isolated peptide comprises amino acid sequence SEQ ID NO:6.
25. The composition of claim 23 , wherein the isolated peptide comprises amino acid sequence SEQ ID NO:7.
26. The composition of claim 23 , wherein the isolated peptide is an isolated antibody or antibody fragment.
27. The composition of claim 26 , wherein the isolated antibody or antibody fragment is an intact soluble monoclonal antibody.
28. The composition of claim 26 , wherein the isolated antibody or antibody fragment is an isolated monoclonal antibody fragment selected from the group consisting of an F(ab′) 2 fragment, an Fd fragment, and an Fab fragment.
29. The composition of claim 26 , wherein the isolated antibody or antibody fragment enhances opsonophagocytosis of P. aeruginosa.
30. The composition of claim 23 , wherein the isolated peptide is conjugated to a detectable label.
31. The composition of claim 23 , wherein the composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier.
32. The composition of claim 26 , wherein the isolated antibody or antibody fragment is present in an effective amount for inhibiting a P. aeruginosa infection.
33. The composition of claim 26 , wherein the isolated antibody or antibody fragment is present in an effective amount for inhibiting a disorder associated with the presence of P. aeruginosa infection.
34. The composition of claim 31 , wherein the isolated peptide is present in an effective amount for detecting P. aeruginosa in a sample in or from a subject.
35. The composition of claim 26 , wherein the isolated antibody or antibody fragment is a human antibody or antibody fragment.
36. The composition of claim 26 , wherein the isolated antibody or antibody fragment is an IgG, IgA or IgM isotype.
37. A method for detecting P. aeruginosa in a subject comprising
determining a test level of binding of the isolated peptide of claim 23 to a sample in or from a subject, and
comparing the test level of binding to a control,
wherein a test level of binding that is greater than the control is indicative of the presence of P. aeruginosa in the sample.
38. A method for treating a subject having, or at risk of developing, a P. aeruginosa infection comprising
administering to a subject in need of such treatment the isolated peptide of claim 23 in an amount effective to inhibit a P. aeruginosa infection.
39. The composition of claim 23 , wherein the isolated antibody fragment is an Fv.