Anti-pseudomonas Psl binding molecules and uses thereof
The disclosure relates to an anti- Pseudomonas PSL binding molecule and uses thereof, in particular, in prevention and treatment of Pseudomonas infection. Furthermore, the disclosure provides compositions and methods for preventing and treating Pseudomonas infection.
1. An isolated antibody or antigen-binding fragment thereof which specifically binds to Pseudomonas Psl polysaccharide, wherein the antibody or antigen-binding fragment thereof promotes opsonophagocytic killing (OPK) of P. aeruginosa , and wherein the isolated antibody or antigen-binding fragment thereof specifically binds to the same Pseudomonas Psl epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and the light chain variable region (VL) of WapR-004RAD, which comprises SEQ ID NO: 74 and SEQ ID NO: 12, respectively.
2. An isolated antibody or antigen-binding fragment thereof which specifically binds to Pseudomonas Psl polysaccharide, wherein the antibody or antigen-binding fragment thereof promotes opsonophagocytic killing (OPK) of P. aeruginosa , and wherein the isolated antibody or antigen-binding fragment thereof competitively inhibits Pseudomonas Psl binding by an antibody r antigen-binding fragment comprising the heavy chain variable region (VH) and the light chain variable region (VL) of WapR-004RAD, which comprises SEQ ID NO: 74 and SEQ ID NO: 12, respectively.
3. An isolated antibody or antigen-binding fragment thereof which specifically binds to Pseudomonas Psl polysaccharide comprising a set of complementarity determining regions (CDRs) VHCDR1, VHCDR2, VHCDR3, VLCDR1, VLCDR2 and VLCDR3 comprising SEQ ID NOs: 47, 48, 75, 50, 51, and 52.
4. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is humanized, chimeric or fully human.
5. The antibody or antigen-binding fragment thereof of claim 4 , wherein the antibody or antigen-binding fragment thereof is a Fab fragment, a Fab′ fragment, a F(ab)2 fragment or a single chain Fv (scFv).
6. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is monoclonal.
7. The antibody or antigen-binding fragment thereof of claim 1 , further comprising a pharmaceutically acceptable carrier.
8. The antibody or antigen-binding fragment thereof of claim 3 further comprising a pharmaceutically acceptable carrier.
9. The antibody or antigen-binding fragment thereof of claim 2 , wherein the antibody or antigen-binding fragment thereof is humanized, chimeric or fully human.
10. The antibody or antigen-binding fragment thereof of claim 9 , wherein the antibody or antigen-binding fragment thereof is a Fab fragment, a Fab′ fragment, a F(ab)2 fragment or a single chain Fv (scFv).
11. The antibody or antigen-binding fragment thereof of claim 2 , wherein the antibody or antigen-binding fragment thereof is monoclonal.
12. The antibody or antigen-binding fragment thereof of claim 2 , further comprising a pharmaceutically acceptable carrier.
13. The isolated antibody or antigen-binding fragment thereof of claim 3 comprising a heavy chain variable region (VH) comprising SEQ ID NO: 74 and a light chain variable region (VL) comprising SEQ ID NO: 12.
14. The antibody or antigen-binding fragment thereof of claim 13 further comprising a pharmaceutically acceptable carrier.