Anti-O1 antibodies and uses thereof
The present disclosure provides binding proteins (e.g., antibodies or antigen binding fragments thereof) that specifically bind to Klebsiella pneumoniae O1 and induce opsonophagocytic killing of Klebsiella (e.g., Klebsiella pneumoniae ). The present disclosure also provides methods of reducing Klebsiella (e.g., Klebsiella pneumoniae ) or treating or preventing Klebsiella (e.g., Klebsiella pneumoniae ) infection in a subject comprising administering the Klebsiella pneumoniae O1 binding proteins, (e.g., antibodies or antigen-binding fragments thereof) to the subject.
1. An isolated antigen binding protein that specifically binds to Klebsiella pneumoniae O1 antigen comprising a set of Complementarity-Determining Regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 1, 2, 3, 4, 5, and 7, respectively.
2. The isolated antigen binding protein of claim 1 , wherein the LCDR2 comprises the amino acid sequences of SEQ ID NO:6.
3. An isolated antigen binding protein that specifically binds to Klebsiella pneumoniae O1 antigen, wherein the antigen binding protein comprises a VH comprising the amino acid sequence of SEQ ID NO:8 and a VL comprising the amino acid sequence of SEQ ID NO:9.
4. The antigen binding protein of claim 1 , wherein said antigen binding protein is an antibody.
5. The antigen binding protein of claim 1 , wherein said antigen binding protein is an antigen-binding fragment of an antibody.
6. The antigen binding protein of claim 3 , wherein said antigen binding protein is an antibody.
7. The antigen binding protein of claim 3 , wherein said antigen binding protein is an antigen-binding fragment of an antibody.
8. The antigen binding protein of claim 1 , which is a monoclonal antibody.
9. The antigen binding protein of claim 3 , which is a monoclonal antibody.
10. An antigen binding protein produced by (i) culturing a host cell comprising a nucleic acid molecule encoding the antigen binding protein of claim 1 ; and (ii) isolating said antigen binding protein thereof from said cultured host cell.
11. An antigen binding protein produced by (i) culturing a host cell comprising a nucleic acid molecule encoding the antigen binding protein of claim 3 ; and (ii) isolating said antigen binding protein thereof from said cultured host cell.
12. A pharmaceutical composition comprising the antigen binding protein of claim 1 and a pharmaceutically acceptable excipient.
13. A pharmaceutical composition comprising the antigen binding protein of claim 3 and a pharmaceutically acceptable excipient.
14. A pharmaceutical composition comprising the antigen binding protein of claim 4 and a pharmaceutically acceptable excipient.
15. A pharmaceutical composition comprising the antigen binding protein of claim 5 and a pharmaceutically acceptable excipient.
16. The pharmaceutical composition comprising the antigen binding protein of claim 6 and a pharmaceutically acceptable excipient.
17. The pharmaceutical composition comprising the antigen binding protein of claim 7 and a pharmaceutically acceptable excipient.
18. The antigen binding protein of claim 1 , wherein said antigen binding protein induces opsonophagocytic killing (OPK) of Klebsiella and kills Klebsiella via complement dependent killing as measured by a serum bactericidal assay.
19. The antigen binding protein of claim 3 , wherein said antigen binding protein induces OPK killing of Klebsiella and kills Klebsiella via complement dependent killing as measured by a serum bactericidal assay.
20. The antigen binding protein of claim 1 , wherein said antigen binding protein does not neutralize lipopolysaccharide (LPS).
21. The antigen binding protein of claim 3 , wherein said antigen binding protein does not neutralize lipopolysaccharide (LPS).
22. The antigen binding protein of claim 18 , wherein said Klebsiella is multi-drug resistant.
23. The antigen binding protein of claim 19 , wherein said Klebsiella is multi-drug resistant.
24. The antigen binding protein of claim 18 , wherein said Klebsiella is susceptible to antibiotics.
25. The antigen binding protein of claim 19 , wherein said Klebsiella is susceptible to antibiotics.