Middle east respiratory syndrome coronavirus neutralizing antibodies and methods of use thereof
The present invention provides antibodies that neutralize MERS-CoV and methods of use thereof. The invented antibody is used to treat MERS-CoV infections and symptoms thereof.
1. An isolated monoclonal antibody, wherein said monoclonal antibody comprises a V H amino acid sequence having SEQ ID NO: 10, and a V L amino acid sequence having SEQ ID NO: 12.
2. The monoclonal antibody of claim 1 , wherein said monoclonal antibody inhibits viral and cell membrane fusion.
3. The monoclonal antibody of claim 1 , wherein said monoclonal antibody competes with the binding of monoclonal antibody 1E9, 1F8, 3B12, 3A1, 3C12, 3B11 or M14D3 to the spike protein.
4. The monoclonal antibody of claim 1 , wherein said monoclonal antibody is a fully human antibody.
5. The monoclonal antibody of claim 1 , wherein said monoclonal antibody blocks the binding of MERS-CoV spike protein to DPP4 receptor.
6. The monoclonal antibody of claim 1 , wherein said monoclonal antibody is produced in a plant.
7. An isolated scFv antibody, wherein said antibody comprises a V H amino acid sequence having SEQ ID NO: 10, and a V L amino acid sequence having SEQ ID NO: 12.
8. The scFv antibody of claim 7 , wherein said scFv antibody inhibits viral and cell membrane fusion.
9. The scFv antibody of claim 7 , wherein said scFv antibody competes with the binding of monoclonal antibody 1E9, 1F8, 3B12, 3A1, 3C12, 3B11 or M14D3 to the spike protein.
10. The scFv antibody of claim 7 , wherein said monoclonal antibody blocks the binding of MERS-CoV spike protein to DPP4 receptor.
11. A method of treating a disease or disorder caused by a Middle East Respiratory Syndrome coronavirus (MERS-CoV), the method comprising administering to a person at risk of suffering from said disease or disorder, a therapeutically effective amount of the monoclonal antibody of claim 1 or the scFv antibody of claim 7 .
12. The method of claim 11 , wherein the method further comprises administering an anti-viral drug, a viral entry inhibitor or a viral attachment inhibitor.
13. The method of claim 11 , wherein the method comprises administering two or more antibodies specific to MERS-CoV.
14. The method of claim 11 , wherein said antibody is administered prior to or after exposure to MERS-CoV.
15. The method of claim 11 , wherein said antibody is administered at a dose sufficient to neutralize said MERS-CoV.
16. A method of delaying the onset of one or more symptoms of a MERS-CoV infection, comprising administering to a person at risk of suffering from said infection, a therapeutically effective amount of the monoclonal antibody of claim 1 or the scFv antibody of claim 7 .
17. A composition comprising the monoclonal antibody of claim 1 or the scFv antibody of claim 7 , and a carrier.
18. A method of detecting the presence of MERS-CoV in a sample, the method comprising:
a) contacting the sample with the monoclonal antibody of claim 1 or the scFv antibody of claim 7 ; and
b) detecting the presence or absence of an antibody-antigen complex, thereby detecting the presence of MERS-CoV in a sample.
19. The method of claim 18 , wherein the detecting occurs in vivo.
20. The method of claim 18 , wherein the sample is obtained from blood, hair, cheek scraping, saliva, biopsy, or semen.
21. The monoclonal antibody of claim 1 , wherein said monoclonal antibody binds to an epitope in the receptor binding domain (RBD) of the spike protein of a Middle East Respiratory Syndrome coronavirus (MERS-CoV) and neutralizes MERS-CoV.
22. The monoclonal antibody of claim 21 , wherein said epitope is non-linear.
23. The monoclonal antibody of claim 21 , wherein said epitope comprises a region within amino acids 349-590 of the spike protein when numbered in accordance with SEQ ID NO: 58.
24. The monoclonal antibody of claim 21 , wherein the epitope comprises at least one amino acid at position 506, 512, 540, 542 or 547 of the spike protein when numbered in accordance with SEQ ID NO: 58.
25. The scFv antibody of claim 7 , wherein said monoclonal antibody binds to an epitope in the receptor binding domain (RBD) of the spike protein of a Middle East Respiratory Syndrome coronavirus (MERS-CoV) and neutralizes MERS-CoV.
26. The scFv antibody of claim 25 , wherein said epitope is non-linear.
27. The scFv antibody of claim 25 , wherein said epitope comprises a region within amino acids 349-590 of the spike protein when numbered in accordance with SEQ ID NO: 58.
28. The antibody of claim 25 , wherein the epitope comprises at least one amino acid at position 506, 512, 540, 542 or 547 of the spike protein when numbered in accordance with SEQ ID NO: 58.
29. An isolated monoclonal antibody, wherein said monoclonal antibody comprises a heavy chain with three CDRs comprising the amino acid sequences GGTFSSYA (SEQ ID NO:35), IIPIFGKA (SEQ ID NO:36), and ARDQGISANFKDAFDI (SEQ ID NO:37]) respectively and a light chain with three CDRs comprising the amino acid sequences ESVGSN (SEQ ID NO:52]), GAS (SEQ ID NO:53]), and QQYNNWPLT (SEQ ID NO:54) respectively.
30. The monoclonal antibody of claim 29 , wherein said monoclonal antibody binds to an epitope in the receptor binding domain (RBD) of the spike protein of a Middle East Respiratory Syndrome coronavirus (MERS-CoV) and neutralizes MERS-CoV.
31. The monoclonal antibody of claim 30 , wherein said epitope is non-linear.
32. The monoclonal antibody of claim 30 , wherein said epitope comprises a region within amino acids 349-590 of the spike protein when numbered in accordance with SEQ ID NO: 58.
33. The monoclonal antibody of claim 30 , wherein the epitope comprises at least one amino acid at position 506, 512, 540, 542 or 547 of the spike protein when numbered in accordance with SEQ ID NO: 58.