Human monoclonal antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
The present disclosure is directed to antibodies binding to and neutralizing the coronavirus designated SARS-CoV-2 and methods for use thereof.
1. An isolated antibody or antibody fragment that binds to a SARS-CoV-2 surface spike protein, wherein the antibody or fragment comprises
(a) a CDRH1 comprising the amino acid sequence of SEQ ID NO:59, a CDRH2 comprising the amino acid sequence of SEQ ID NO:60, a CDRH3 comprising the amino acid sequence of SEQ ID NO:61, a CDRL1 comprising the amino acid sequence of SEQ ID NO:89, a CDRH2 comprising the amino acid sequence of SEQ ID NO:90, a CDRH3 comprising the amino acid sequence of SEQ ID NO:91;
(b) a CDRH1 comprising the amino acid sequence of SEQ ID NO:68, a CDRH2 comprising the amino acid sequence of SEQ ID NO:69, a CDRH3 comprising the amino acid sequence of SEQ ID NO:70, a CDRL1 comprising the amino acid sequence of SEQ ID NO:98, a CDRH2 comprising the amino acid sequence of SEQ ID NO:99, a CDRH3 comprising the amino acid sequence of SEQ ID NO:100;
(c) a CDRH1 comprising the amino acid sequence of SEQ ID NO:41, a CDRH2 comprising the amino acid sequence of SEQ ID NO:42, a CDRH3 comprising the amino acid sequence of SEQ ID NO:43, a CDRL1 comprising the amino acid sequence of SEQ ID NO:71, a CDRH2 comprising the amino acid sequence of SEQ ID NO:72, a CDRH3 comprising the amino acid sequence of SEQ ID NO:73;
(d) a CDRH1 comprising the amino acid sequence of SEQ ID NO:44, a CDRH2 comprising the amino acid sequence of SEQ ID NO:45, a CDRH3 comprising the amino acid sequence of SEQ ID NO:46, a CDRL1 comprising the amino acid sequence of SEQ ID NO:74, a CDRH2 comprising the amino acid sequence of SEQ ID NO:75, a CDRH3 comprising the amino acid sequence of SEQ ID NO:76;
(e) a CDRH1 comprising the amino acid sequence of SEQ ID NO:47, a CDRH2 comprising the amino acid sequence of SEQ ID NO:48, a CDRH3 comprising the amino acid sequence of SEQ ID NO:49, a CDRL1 comprising the amino acid sequence of SEQ ID NO:77, a CDRH2 comprising the amino acid sequence of SEQ ID NO:78, a CDRH3 comprising the amino acid sequence of SEQ ID NO:79;
(f) a CDRH1 comprising the amino acid sequence of SEQ ID NO:50, a CDRH2 comprising the amino acid sequence of SEQ ID NO:51, a CDRH3 comprising the amino acid sequence of SEQ ID NO:52, a CDRL1 comprising the amino acid sequence of SEQ ID NO:80, a CDRH2 comprising the amino acid sequence of SEQ ID NO:81, a CDRH3 comprising the amino acid sequence of SEQ ID NO:82;
(g) a CDRH1 comprising the amino acid sequence of SEQ ID NO:53, a CDRH2 comprising the amino acid sequence of SEQ ID NO:54, a CDRH3 comprising the amino acid sequence of SEQ ID NO:55, a CDRL1 comprising the amino acid sequence of SEQ ID NO:83, a CDRH2 comprising the amino acid sequence of SEQ ID NO:84, a CDRH3 comprising the amino acid sequence of SEQ ID NO:85;
(h) a CDRH1 comprising the amino acid sequence of SEQ ID NO:56, a CDRH2 comprising the amino acid sequence of SEQ ID NO:57 a CDRH3 comprising the amino acid sequence of SEQ ID NO:58, a CDRL1 comprising the amino acid sequence of SEQ ID NO:86, a CDRH2 comprising the amino acid sequence of SEQ ID NO:87, a CDRH3 comprising the amino acid sequence of SEQ ID NO:88;
(i) a CDRH1 comprising the amino acid sequence of SEQ ID NO:62, a CDRH2 comprising the amino acid sequence of SEQ ID NO:63 a CDRH3 comprising the amino acid sequence of SEQ ID NO:64, a CDRL1 comprising the amino acid sequence of SEQ ID NO:65, a CDRH2 comprising the amino acid sequence of SEQ ID NO:66, a CDRH3 comprising the amino acid sequence of SEQ ID NO:67; or
(j) a CDRH1 comprising the amino acid sequence of SEQ ID NO:65, a CDRH2 comprising the amino acid sequence of SEQ ID NO:66, a CDRH3 comprising the amino acid sequence of SEQ ID NO:67, a CDRL1 comprising the amino acid sequence of SEQ ID NO:95, a CDRH2 comprising the amino acid sequence of SEQ ID NO:96, a CDRH3 comprising the amino acid sequence of SEQ ID NO:97.
2. The antibody or antibody fragment of claim 1 , wherein the antibody or fragment comprises
(a) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:33 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:34;
(b) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:39 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:40;
(c) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:21 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:22;
(d) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:23 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:24;
(e) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:25 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:26;
(f) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:27 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:28;
(g) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:29 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:30;
(h) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:31 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:32;
(i) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:35 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:36; or
(j) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:37 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:38.
3. The antibody or antibody fragment of claim 1 , wherein the antibody or fragment is monoclonal.
4. The antibody or antibody fragment of claim 1 , wherein the antibody or fragment comprises a YTE mutation.
5. The antibody or antibody fragment of claim 1 , wherein the antibody or fragment is an IgG.
6. The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment is able to bind RBD in the “up” and “down” conformations.
7. The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment is able to bind RBD in the “up” conformation and is not able to bind RBD in the “down” conformation.
8. The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment further comprises a detectable label.
9. A vaccine formulation comprising the antibody or antibody fragment of claim 1 .
10. The vaccine formulation of claim 9 , further comprising a second antibody or antibody fragment that binds to a SARS-CoV-2 surface spike protein.
11. A pharmaceutically acceptable composition or kit comprising a first antibody or antibody fragment that binds to a SARS-CoV-2 surface spike protein and a second antibody or antibody fragment that binds to a SAR-CoV-2 surface spike protein, wherein the first antibody or antibody fragment comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO:59, a CDRH2 comprising the amino acid sequence of SEQ ID NO:60, a CDRH3 comprising the amino acid sequence of SEQ ID NO:61, a CDRL1 comprising the amino acid sequence of SEQ ID NO:89, a CDRH2 comprising the amino acid sequence of SEQ ID NO:90, a CDRH3 comprising the amino acid sequence of SEQ ID NO:91, and wherein the second antibody or antibody fragment comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO:68, a CDRH2 comprising the amino acid sequence of SEQ ID NO:69, a CDRH3 comprising the amino acid sequence of SEQ ID NO:70, a CDRL1 comprising the amino acid sequence of SEQ ID NO:98, a CDRH2 comprising the amino acid sequence of SEQ ID NO:99, a CDRH3 comprising the amino acid sequence of SEQ ID NO:100.
12. The pharmaceutically acceptable composition of claim 11 , wherein the first antibody or antibody fragment comprises a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:33 and a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:34, and wherein the second antibody or antibody fragment comprises a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:39 and a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:40.
13. The pharmaceutically acceptable composition of claim 12 , wherein the first antibody comprises a YTE mutation, and wherein the second antibody comprises a YTE mutation.
14. The pharmaceutically acceptable composition of claim 13 , wherein the first antibody is an IgG1, and wherein the second antibody is an IgG1.
15. The antibody or antibody fragment of claim 1 , wherein the antibody or fragment is a recombinant IgG antibody or antibody fragment comprising an Fc portion, and wherein the Fc portion is a mutated Fc portion comprising a mutation selected from the group consisting of a mutation that alters FcR interactions, and a mutation that increases half-life and/or increase therapeutic efficacy, or a combination thereof.
16. The antibody or antibody fragment of claim 15 , wherein the mutation of the mutated Fc portion is selected from the group consisting of LALA, LALA PG, N297, GASD/ALIE, DHS, YTE and LS, or a combination thereof.
17. An isolated antibody or antibody fragment that binds to a SARS-CoV-2 surface spike protein, wherein the antibody or fragment comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO:59, a CDRH2 comprising the amino acid sequence of SEQ ID NO:60, a CDRH3 comprising the amino acid sequence of SEQ ID NO:61, a CDRL1 comprising the amino acid sequence of SEQ ID NO:89, a CDRH2 comprising the amino acid sequence of SEQ ID NO:90, a CDRH3 comprising the amino acid sequence of SEQ ID NO:91.
18. The antibody or antibody fragment of claim 17 , wherein the antibody or fragment comprises a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:33 and a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:34.
19. The antibody or antibody fragment of claim 18 , wherein the antibody is an IgG1.
20. The antibody or antibody fragment of claim 18 , wherein the antibody comprises a YTE mutation.
21. The antibody or antibody fragment of claim 20 , wherein the antibody is an IgG1.
22. An isolated antibody or antibody fragment that binds to a SARS-CoV-2 surface spike protein, wherein the antibody or fragment comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO:68, a CDRH2 comprising the amino acid sequence of SEQ ID NO:69, a CDRH3 comprising the amino acid sequence of SEQ ID NO:70, a CDRL1 comprising the amino acid sequence of SEQ ID NO:98, a CDRH2 comprising the amino acid sequence of SEQ ID NO:99, a CDRH3 comprising the amino acid sequence of SEQ ID NO:100.
23. The antibody or antibody fragment of claim 22 , wherein the antibody or fragment comprises a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:39 and a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:40.
24. The antibody or antibody fragment of claim 23 , wherein the antibody is an IgG1.
25. The antibody or antibody fragment of claim 23 , wherein the antibody comprises a YTE mutation.
26. The antibody or antibody fragment of claim 25 , wherein the antibody is an IgG1.