Antibodies that bind the spike protein of SARS-CoV-2
The present disclosure provides antibodies and antigen-binding fragments thereof that specifically bind to the spike protein of SARS-COV-2 and methods of making and using the same. The antibodies can be used, for example, in prophylaxis, post-exposure prophylaxis, or treatment of SARS-COV-2 infection. The antibodies can also be used to detect SARS-COV-2, e.g., an infection in subject.
1 . An antibody or antigen-binding fragment thereof that specifically binds to the spike protein of SARS-COV-2, wherein the antibody or antigen-binding fragment comprises the VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, and VL-CDR3 of SEQ ID NOs: 31, 32, 37, 34, 35, and 36, respectively.
2 . The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment comprises:
a variable heavy chain (VH) comprising the amino acid sequence of SEQ ID NO:63 and a variable light chain (VL) comprising the amino acid sequence of SEQ ID NO:61.
3 . The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof neutralizes SARS-COV-2 BA.1, SARS-CoV-2 BA1.1, SARS-COV-2 BA.2, and SARS-COV-2 D614G pseudovirus with an EC50 of 100 ng/ml or less.
4 . The antibody or antigen-binding fragment thereof of claim 3 , wherein the antibody or antigen-binding fragment is fully human.
5 . The antibody or antigen-binding fragment thereof of claim 2 , wherein the antibody or antigen-binding fragment comprises a human IgGλ light chain constant region.
6 . The antibody or antigen-binding fragment thereof of claim 2 , wherein the antibody or antigen-binding fragment comprises a human IgG1 heavy chain constant region.
7 . The antibody or antigen-binding fragment thereof of claim 2 , wherein the antibody or antigen-binding fragment comprises (i) a human IgG1 heavy chain constant region and (ii) a human IgGκ light chain constant region.
8 . The antibody or antigen-binding fragment thereof of claim 7 , wherein the antibody or antigen-binding fragment comprises a heavy chain constant region comprising a YTE mutation.
9 . The antibody or antigen-binding fragment thereof of claim 8 , wherein the antibody or antigen-binding fragment comprises a heavy chain constant region comprising a TM mutation.
10 . The antibody or antigen-binding fragment thereof of claim 2 , which is a full-length antibody.
11 . A composition comprising the antibody or antigen-binding fragment thereof of claim 1 , wherein the composition is a pharmaceutical composition further comprising a pharmaceutically acceptable excipient.
12 . A composition comprising the antibody or antigen-binding fragment thereof of claim 2 , wherein the composition is a pharmaceutical composition further comprising a pharmaceutically acceptable excipient.
13 . A composition comprising the antibody or antigen-binding fragment thereof of claim 9 , wherein the composition is a pharmaceutical composition further comprising a pharmaceutically acceptable excipient.
14 . An antibody that specifically binds to the spike protein of SARS-CoV-2 and comprises a variable heavy chain (VH) comprising the amino acid sequence of SEQ ID NO: 63 and a variable light chain (VL) comprising the amino acid sequence of SEQ ID NO:61, wherein the antibody further comprises (i) a human heavy chain constant region comprising the amino acid sequence of SEQ ID NO:66 and (ii) a human IgGκ light chain constant region.
15 . A composition comprising the antibody or antigen-binding fragment thereof of claim 14 , wherein the composition is a pharmaceutical composition further comprising a pharmaceutically acceptable excipient.