Ebola virus glycoprotein-specific monoclonal antibodies and uses thereof
AssigneeThe U.S.A., as represented by the Secretary, Department of Health and Human Services
InventorsNancy J. Sullivan, John Misasi, Brandon Dekosky, Kendra Elizabeth Leigh
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Abstract
Human monoclonal antibodies that specifically bind Ebola virus glycoprotein with nanomolar affinity are described. The monoclonal antibodies were isolated by bulk sorting of plasmablasts from a human Ebola virus vaccinee and pairing of the immunoglobulin heavy and light chain genes using emulsion PCR. The paired immunoglobulin genes were expressed using Fab yeast display to screen and characterize the antibodies. The Ebola virus-specific monoclonal antibodies can be used, for example, to diagnose and treat Ebola virus infection or Ebola virus disease in a subject.
Claims33
A monoclonal antibody that specifically binds to Ebola virus (EBOV) glycoprotein (GP), comprising a variable heavy (VH) domain and a variable light (VL) domain, wherein:
- (i) the VH domain comprises the VH complementarity determining region (HCDR)1, HCDR2, and HCDR3 sequences of SEQ ID NO:
- 2 and the VL domain comprises the VL complementarity determining region (LCDR)1, LCDR2, and LCDR3 sequences of SEQ ID NO:
- 4;
- (ii) the VH domain comprises the HCDR1, HCDR2 and HCDR3 sequences of SEQ ID NO:
- 6 and the VL domain comprises the LCDR1, LCDR2 and LCDR3 sequences of SEQ ID NO:
- 8;
- (iii) the VH domain comprises the HCDR1, HCDR2 and HCDR3 sequences of SEQ ID NO:
- 10 and the VL domain comprises the LCDR1, LCDR2 and LCDR3 sequences of SEQ ID NO:
- 12;
- (iv) the VH domain comprises the HCDR1, HCDR2 and HCDR3 sequences of SEQ ID NO:
- 14 and the VL domain comprises the LCDR1, LCDR2 and LCDR3 sequences of SEQ ID NO:
- 16;
- (v) the VH domain comprises the HCDR1, HCDR2 and HCDR3 sequences of SEQ ID NO:
- 18 and the VL domain comprises the LCDR1, LCDR2 and LCDR3 sequences of SEQ ID NO:
- 20;
- (vi) the VH domain comprises the HCDR1, HCDR2 and HCDR3 sequences of SEQ ID NO:
- 22 and the VL domain comprises the LCDR1, LCDR2 and LCDR3 sequences of SEQ ID NO:
- 24;
- (vii) the VH domain comprises the HCDR1, HCDR2 and HCDR3 sequences of SEQ ID NO:
- 26 and the VL domain comprises the LCDR1, LCDR2 and LCDR3 sequences of SEQ ID NO:
- 28;
- or
- (viii) the VH domain comprises the HCDR1, HCDR2 and HCDR3 sequences of SEQ ID NO:
- 30 and the VL domain comprises the LCDR1, LCDR2 and LCDR3 sequences of SEQ ID NO:
- 32.
The monoclonal antibody of wherein:
- the amino acid sequence of the VH domain comprises SEQ ID NO:
- 2 and the amino acid sequence of the VL domain comprises SEQ ID NO:
- 4;
- the amino acid sequence of the VH domain comprises SEQ ID NO:
- 6 and the amino acid sequence of the VL domain comprises SEQ ID NO:
- 8;
- the amino acid sequence of the VH domain comprises SEQ ID NO:
- 10 and the amino acid sequence of the VL domain comprises SEQ ID NO:
- 12;
- the amino acid sequence of the VH domain comprises SEQ ID NO:
- 14 and the amino acid sequence of the VL domain comprises SEQ ID NO:
- 16;
- the amino acid sequence of the VH domain comprises SEQ ID NO:
- 18 and the amino acid sequence of the VL domain comprises SEQ ID NO:
- 20;
- the amino acid sequence of the VH domain comprises SEQ ID NO:
- 22 and the amino acid sequence of the VL domain comprises SEQ ID NO:
- 24;
- the amino acid sequence of the VH domain comprises SEQ ID NO:
- 26 and the amino acid sequence of the VL domain comprises SEQ ID NO:
- 28;
- or
- the amino acid sequence of the VH domain comprises SEQ ID NO:
- 30 and the amino acid sequence of the VL domain comprises SEQ ID NO:
- 32.
The monoclonal antibody of wherein the antibody is an IgG, IgM or IgA.
(canceled)
22-23. (canceled)
(canceled)
Dependencies are inferred from the claim text.