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. An antibody comprising the amino acid sequences of SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15, and having a non-IgG2 constant region.
2. The antibody of claim 1 , wherein the antibody has an IgG1 constant region.
3. The antibody of claim 1 , wherein the antibody comprises the amino acid sequence of SEQ ID NO:3.
4. The antibody of claim 1 , wherein the antibody comprises the amino acid sequences of SEQ ID NO:16, SEQ ID NO:17 and SEQ ID NO:18.
5. The antibody of claim 1 , wherein the antibody comprises the amino acid sequence of SEQ ID NO:4.
6. The antibody of claim 1 , wherein the antibody is isolated.
7. The antibody of claim 1 , wherein the antibody is a monoclonal antibody.
8. A pharmaceutical composition comprising the antibody of claim 1 .
9. An antigen-binding antibody fragment of the antibody of claim 1 , wherein the fragment comprises amino acid sequence of the constant region.
10. A pharmaceutical composition comprising the antigen-binding antibody fragment of claim 9 .
11. A method of treating a subject having or at risk of developing an infection by a bacterial strain expressing PNAG comprising
administering to a subject in need of such treatment an antibody of claim 1 in an effective amount.
12. A method of treating a subject having or at risk of developing an infection by a bacterial strain expressing PNAG comprising
administering to a subject in need of such treatment an antigen-binding antibody fragment of claim 9 in an effective amount.