Antibodies against SARS-CoV-2 and methods of using the same
The instant disclosure provides antibodies and antigen-binding fragments thereof that can bind to a SARS-CoV-2 antigen and, in certain embodiments, are capable of neutralizing a SARS-CoV-2 infection. Also provided are polynucleotides that encode an antibody or antigen-binding fragment, vectors and host cells that comprise a polynucleotide, pharmaceutical compositions, and methods of using the presently disclosed antibodies, antigen-binding fragments, polynucleotides, vectors, host cells, and compositions to treat or diagnose a SARS-CoV-2 infection.
1. An isolated antibody, or an antigen-binding fragment thereof, comprising a heavy chain variable domain (VH) that comprises the complementarity determining region (CDR)H1 amino acid sequence set forth in SEQ ID NO.:106, the CDRH2 amino acid sequence set forth in SEQ ID NO.:121, and the CDRH3 amino acid sequence set forth in SEQ ID NO.:108, and a light chain variable domain (VL) that comprises the CDRL1 amino acid sequence set forth in SEQ ID NO.:169, the CDRL2 amino acid sequence set forth in SEQ ID NO.:170, and the CDRL3 amino acid sequence set forth in SEQ ID NO.:171,
wherein the antibody or antigen-binding fragment is capable of binding to a SARS-CoV-2 surface glycoprotein (S): expressed on a cell surface of a host cell; on a SARS-CoV-2 virion; or both.
2. The isolated antibody or antigen-binding fragment of claim 1 , which is capable of binding to a surface glycoprotein (S) of:
(i) a SARS-CoV-2 Wuhan-Hu-1 (SEQ ID NO.:165);
(ii) a SARS-CoV-2 B.1.1.7;
(iii) a SARS-CoV-2 B.1.351;
(iv) a SARS-CoV-2 comprising any one or more of the following substitution mutations relative to SEQ ID NO.:165: N501Y; S477N; N439K; L452R; E484K; Y453F; A520S; K417N; K417V; S494P; N501T; 5477R; V367F; P384L; A522S; A522V; V382L; P330S; T478I; S477I; P479S; or
(v) any combination of (i)-(iv).
3. The isolated antibody or antigen-binding fragment of claim 1 , which is capable of neutralizing a SARS-CoV-2 infection:
(i) in an in vitro model of infection;
(ii) in an in vivo animal model of infection;
(iii) in a human; or
(iv) any combination of (i)-(iii).
4. The isolated antibody or antigen-binding fragment of claim 1 , wherein:
(i) the VH comprises or consists of an amino acid sequence having at least 85% identity to the amino acid sequence set forth in SEQ ID NO.:113; and/or
(ii) the VL comprises or consists of an amino acid sequence having at least 85% identity to the amino acid sequence set forth in SEQ ID NO.:168.
5. The isolated antibody or antigen-binding fragment of claim 4 , wherein:
(i) the VH comprises or consists of an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO.:113; and/or
(ii) the VL comprises or consists of an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO.:168.
6. The isolated antibody or antigen-binding fragment of claim 4 , wherein:
(i) the VH comprises or consists of an amino acid sequence having at least 95% identity to the amino acid sequence set forth in SEQ ID NO.:113; and/or
(ii) the VL comprises or consists of an amino acid sequence having at least 95% identity to the amino acid sequence set forth in SEQ ID NO.:168.
7. The isolated antibody or antigen-binding fragment of claim 4 , wherein:
(i) the VH comprises or consists of an amino acid sequence having at least 99% identity to the amino acid sequence set forth in SEQ ID NO.:113; and/or
(ii) the VL comprises or consists of an amino acid sequence having at east 99% identity to the amino acid sequence set forth in SEQ ID NO.:168.
8. The isolated antibody or antigen-binding fragment of claim 1 , which is capable of inhibiting an interaction between:
(i) SARS-CoV-2 and a human DC-SIGN;
(ii) SARS-CoV-2 and a human L-SIGN;
(iii) SARS-CoV-2 and a human SIGLEC-1; or
(iv) any combination of (i)-(iii).
9. The isolated antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises a human antibody, a monoclonal antibody, a purified antibody, a single chain antibody, a Fab, a Fab′, a F(ab′)2, a Fv, a scFv, or a scFab.
10. The isolated antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment further comprises a Fc polypeptide or a fragment thereof.
11. The isolated antibody or antigen-binding fragment of claim 10 , wherein the Fc polypeptide or fragment thereof comprises:
(i) a mutation that enhances binding to a FcRn as compared to a reference Fc polypeptide that does not comprise the mutation; and/or
(ii) a mutation that enhances binding to a FcγR as compared to a reference Fc polypeptide that does not comprise the mutation.
12. The isolated antibody or antigen-binding fragment of claim 11 , wherein the mutation that enhances binding to a FcRn comprises:
(i) M428L/N434S;
(ii) M252Y/S254T/T256E;
(iii) T250Q/M428L;
(iv) P257I/Q311I;
(v) P257I/N434H;
(vi) D376V/N434H;
(vii) T307A/E380A/N434A; or
(viii) any combination of (i)-(vii).
13. The isolated antibody or antigen-binding fragment of claim 12 , wherein the mutation that enhances binding to FcRn comprises M428L/N434S.
14. The isolated antibody or antigen-binding fragment of claim 12 , wherein the mutation that enhances binding to a FcγR comprises S239D, I332E, A330L, G236A, or any combination thereof.
15. The isolated antibody or antigen-binding fragment of claim 14 , wherein the mutation that enhances binding to a FcγR comprises:
(i) S239D/I332E;
(ii) S239D/A330L/I332E;
(iii) G236A/S239D/I332E; or
(iv) G236A/A330L/I332E.
16. The isolated antibody or antigen-binding fragment of claim 1 , which is a IgG, IgA, IgM, IgE, or IgD isotype.
17. The isolated antibody or antigen-binding fragment of claim 1 , further comprising a CH1-CH3 that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:265 or 266.
18. An isolated antibody, or an antigen-binding fragment thereof, comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:113 and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:168.
19. The isolated antibody or antigen-binding fragment of claim 18 , which is capable of neutralizing a SARS-CoV-2 infection:
(i) in an in vitro model of infection;
(ii) in an in vivo animal model of infection;
(iii) in a human; or
(iv) any combination of (i)-(iii).
20. The isolated antibody or antigen-binding fragment of claim 18 , which is capable of inhibiting an interaction between:
(i) SARS-CoV-2 and a human DC-SIGN;
(ii) SARS-CoV-2 and a human L-SIGN;
(iii) SARS-CoV-2 and a human SIGLEC-1; or
(iv) any combination of (i)-(iii).
21. The isolated antibody or antigen-binding fragment of claim 18 , wherein the antibody or antigen-binding fragment further comprises a Fc polypeptide or a fragment thereof.
22. The isolated antibody or antigen-binding fragment of claim 21 , which is a IgG, IgA, IgM, IgE, or IgD isotype.
23. The isolated antibody or antigen-binding fragment of claim 21 , wherein the Fc polypeptide or fragment thereof comprises:
(i) a mutation that enhances binding to a FcRn as compared to a reference Fc polypeptide that does not comprise the mutation; and/or
(ii) a mutation that enhances binding to a FcγR as compared to a reference Fc polypeptide that does not comprise the mutation.
24. The isolated antibody or antigen-binding fragment of claim 23 , wherein the mutation that enhances binding to a FcRn comprises:
(i) M428L/N434S;
(ii) M252Y/S254T/T256E;
(iii) T250Q/M428L;
(iv) P257I/Q311I;
(v) P257I/N434H;
(vi) D376V/N434H;
(vii) T307A/E380A/N434A; or
(viii) any combination of (i)-(vii).
25. The isolated antibody or antigen-binding fragment of claim 24 , wherein the mutation that enhances binding to FcRn comprises M428L/N434S.
26. The isolated antibody or antigen-binding fragment of claim 23 , wherein the mutation that enhances binding to a FcγR comprises S239D, I332E, A330L, G236A, or any combination thereof.
27. The isolated antibody or antigen-binding fragment of claim 26 , wherein the mutation that enhances binding to a FcγR comprises:
(i) S239D/I332E;
(ii) S239D/A330L/I332E;
(iii) G236A/S239D/I332E; or
(iv) G236A/A330L/I332E.
28. The isolated antibody or antigen-binding fragment of claim 18 , further comprising a CH1-CH3 that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:265 or 266.
29. An isolated antibody that comprises:
(i) a heavy chain comprising (i)(1) a VH that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:113, and (i)(2) a CH1-CH3 that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:173; and
(ii) a light chain comprising (ii)(1) a VL that comprises or consists of the amino acid sequence set forth in SEQ ID NO.: 168, and (ii)(2) a CL that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:174.
30. An isolated antibody that comprises:
(i) a heavy chain comprising (i)(1) a VH that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:113, and (i)(2) a CH1-CH3 that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:175; and
(ii) a light chain comprising (ii)(1) a VL that comprises or consists of the amino acid sequence set forth in SEQ ID NO.: 168, and (ii)(2) a CL that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:174.