Anti-OSPA antibodies and methods of use
The invention provides anti-OspA antibodies and methods of using the same.
1. An isolated antibody that specifically binds to outer surface protein A (OspA), wherein the antibody comprises the following six CDRs:
(a) a CDR-H1 comprising the amino acid sequence of GYSFTSYWIG (SEQ ID NO: 10);
(b) a CDR-H2 comprising the amino acid sequence of FIYPGDSDTRYSPSFQG (SEQ ID NO: 11);
(c) a CDR-H3 comprising the amino acid sequence of ARGILRYFDWFLDY (SEQ ID NO: 4);
(d) a CDR-L1 comprising the amino acid sequence of RASQGISSGSA (SEQ ID NO: 12);
(e) a CDR-L2 comprising the amino acid sequence of DVSSLES (SEQ ID NO: 7); and
(f) a CDR-L3 comprising the amino acid sequence of QQFNSYLLT (SEQ ID NO: 8).
2. The antibody of claim 1 , wherein the antibody comprises (a) a heavy chain variable domain (VH) sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 13; (b) a light chain variable domain (VL) sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 14; or (c) a VH sequence as in (a) and a VL sequence as in (b).
3. An isolated antibody that specifically binds to OspA, wherein the antibody comprises (a) a VH sequence comprising the amino acid sequence of SEQ ID NO: 13 and (b) a VL sequence comprising the amino acid sequence of SEQ ID NO: 14.
4. The antibody of claim 1 , wherein the antibody binds to an epitope comprising amino acid residues 71-105 of OspA (SEQ ID NO: 15).
5. An isolated antibody that specifically binds to OspA, wherein the antibody comprises the following six CDRs:
(a) a CDR-H1 comprising the amino acid sequence of GYKFSSYWIG (SEQ ID NO: 16);
(b) a CDR-H2 comprising the amino acid sequence of IIFPGDSDKRYSPSFQG (SEQ ID NO: 17);
(c) a CDR-H3 comprising the amino acid sequence of ARHITTHTYRGFFDF (SEQ ID NO: 5);
(d) a CDR-L1 comprising the amino acid sequence of RASQDISSALA (SEQ ID NO: 18);
(e) a CDR-L2 comprising the amino acid sequence of DVSSLES (SEQ ID NO: 7); and
(f) a CDR-L3 comprising the amino acid sequence of QQFNGYPHRLT (SEQ ID NO: 9).
6. The antibody of claim 5 , wherein the antibody comprises (a) a VH sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 19; (b) a VL sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 20; or (c) a VH sequence as in (a) and a VL sequence as in (b).
7. An isolated antibody that specifically binds to OspA, wherein the antibody comprises (a) a VH sequence comprising the amino acid sequence of SEQ ID NO: 19 and (b) a VL sequence comprising the amino acid sequence of SEQ ID NO: 20.
8. The antibody of claim 5 , wherein the antibody binds to an epitope comprising amino acid residues 106-141 of OspA (SEQ ID NO: 21).
9. The antibody of claim 1 , wherein the antibody binds to three or more Borrelia species.
10. The antibody of claim 9 , wherein the three or more Borrelia species comprises Borrelia burgdorferi, Borrelia afzelii , and Borrelia garinii.
11. The antibody of claim 10 , wherein the antibody binds to OspA of Borrelia burgdorferi, Borrelia afzelii , and Borrelia garinii with a K D of at least about 10 nM or lower.
12. The antibody of claim 9 , wherein the antibody exhibits borreliacidal activity against Borrelia species comprising Borrelia burgdorferi, Borrelia afzelii , and Borrelia garinii in a borreliacidal assay.
13. An isolated antibody that specifically binds to OspA, wherein the antibody comprises the following six CDRs:
(a) a CDR-H1 comprising the amino acid sequence of GYIFATYWIG (SEQ ID NO: 23);
(b) a CDR-H2 comprising the amino acid sequence of IIYPNDSDTRYSPSFQG (SEQ ID NO: 24);
(c) a CDR-H3 comprising the amino acid sequence of ARTRWYFDL (SEQ ID NO: 25);
(d) a CDR-L1 comprising the amino acid sequence of RASQSVSSSYLA (SEQ ID NO: 26);
(e) a CDR-L2 comprising the amino acid sequence of GASSRAT (SEQ ID NO: 27); and
(f) a CDR-L3 comprising the amino acid sequence of QQYGSSPLT (SEQ ID NO: 28).
14. The antibody of claim 13 , wherein the antibody binds to an epitope comprising amino acid residues 178-273 of OspA (SEQ ID NO: 22).
15. The antibody of claim 13 , wherein the antibody comprises (a) a heavy chain variable domain (VH) sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 29; (b) a light chain variable domain (VL) sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 30; or (c) a VH sequence as in (a) and a VL sequence as in (b).
16. An isolated antibody that specifically binds to OspA, wherein the antibody comprises (a) a VH sequence comprising the amino acid sequence of SEQ ID NO: 29 and (b) a VL sequence comprising the amino acid sequence of SEQ ID NO: 30.
17. The antibody of claim 13 , wherein the antibody binds to OspA of two or more Borrelia species.
18. The antibody of claim 17 , wherein the two or more Borrelia species comprises Borrelia burgdorferi and Borrelia afzelii.
19. The antibody of claim 18 , wherein the antibody binds to OspA of Borrelia burgdorferi and Borrelia afzelii with a K D of at least about 1.2 μM or lower.
20. The antibody of claim 17 , wherein the antibody exhibits borreliacidal activity against Borrelia species comprising Borrelia burgdorferi and Borrelia afzelii in a borreliacidal assay.
21. An isolated antibody that specifically binds to OspA, wherein the antibody comprises the following six CDRs:
(a) a CDR-H1 comprising the amino acid sequence of GFTFRNYWMD (SEQ ID NO: 32);
(b) a CDR-H2 comprising the amino acid sequence of NIKQDGSVKYYVDSVEG (SEQ ID NO: 33);
(c) a CDR-H3 comprising the amino acid sequence of ARDGYSGYDSVGFDI (SEQ ID NO: 34);
(d) a CDR-L1 comprising the amino acid sequence of RASQSVSSSYLA (SEQ ID NO: 35);
(e) a CDR-L2 comprising the amino acid sequence of DTSSRAT (SEQ ID NO: 36); and
(f) a CDR-L3 comprising the amino acid sequence of QQYGSSPYT (SEQ ID NO: 37).
22. The antibody of claim 21 , wherein the antibody comprises (a) a heavy chain variable domain (VH) sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 38; (b) a light chain variable domain (VL) sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 39; or (c) a VH sequence as in (a) and a VL sequence as in (b).
23. An isolated antibody that specifically binds to OspA, wherein the antibody comprises (a) a VH sequence comprising the amino acid sequence of SEQ ID NO: 38 and (b) a VL sequence comprising the amino acid sequence of SEQ ID NO: 39.
24. The antibody of claim 21 , wherein the antibody binds to an epitope comprising amino acid residues 142-177 of OspA (SEQ ID NO: 31).
25. The antibody of claim 21 , wherein the antibody binds to OspA of two or more Borrelia species.
26. The antibody of claim 25 , wherein the one or more Borrelia species comprises Borrelia burgdorferi.
27. The antibody of claim 25 , wherein the antibody binds to OspA of Borrelia burgdorferi with a K D of at least about 5 nM or lower.
28. The antibody of claim 25 , wherein the antibody exhibits borreliacidal activity against Borrelia species comprising Borrelia burgdorferi in a borreliacidal assay.
29. The antibody of claim 1 , wherein the antibody is monoclonal, human, humanized, or chimeric.
30. The antibody of claim 1 , wherein the antibody is an antibody fragment that binds OspA.
31. The antibody of claim 30 , wherein the antibody fragment is selected from the group consisting of Fab, Fab′-SH, Fv, scFv, and (Fab′) 2 fragments.
32. The antibody of claim 1 , wherein the antibody is a full-length antibody.
33. The antibody of claim 1 , wherein the half-life of the antibody is 3 days.
34. A pharmaceutical composition comprising the antibody of claim 1 .
35. An isolated nucleic acid encoding the antibody of claim 1 .
36. A vector comprising the nucleic acid of claim 35 .
37. A host cell comprising the vector of claim 36 .
38. A method of producing an antibody that specifically binds to outer surface protein A (OspA), the method comprising culturing the host cell of claim 37 in a culture medium.
39. A method of treating a subject having a disorder associated with a Borrelia infection comprising administering to the subject a therapeutically effective amount of the antibody of claim 1 , thereby treating the subject.
40. A method of treating a subject at risk of developing a disorder associated with a Borrelia infection comprising administering to the subject a therapeutically effective amount of the antibody of claim 1 , thereby treating the subject.
41. The method of claim 39 , wherein the disorder associated with a Borrelia infection is Lyme borreliosis (Lyme disease).
42. A method of testing a Borrelia vector for the presence of Borrelia , the method comprising contacting a sample from the Borrelia vector with the antibody of claim 1 and determining if binding occurs, wherein binding is indicative of the presence of a Borrelia.
43. A method of decreasing Borrelia load in a Borrelia vector, the method comprising providing the antibody of claim 1 to the Borrelia vector.
44. A method of detecting a Borrelia infection in a subject comprising contacting a body fluid of the subject with the antibody of claim 1 and determining if binding occurs, wherein binding is indicative of the presence of a Borrelia infection.