Extended Table 1.
Classification and structural properties of SARS-CoV-2 RBD-specific antibodies
| Antibody | Reference | IGHV (# of aa SHM) | CDRH3 length (aa)^ | IGLV (# of aa SHM) | CDRL3 length (aa)^ | IC50/IC90 (ng/mL)† | Potential IgG intra-spike Binding§ | Contacts adjacent RBD | Structural Information |
|---|---|---|---|---|---|---|---|---|---|
| Class 1: Blocks ACE2, accessibility of RBD epitope onlv in “up” conformation | |||||||||
| C102 | this study | VH3-53 (2) | 11 | VK3-20 (0) | 9 | 34 / 143 | ??? | ??? | 3.0 Å Fab-RBD |
| C105 | Barnes, et al.26 | VH3-53 (0) | 12 | VL2-8 (1) | 11 | 26.1 / 134 | Yes | No | 3.4 Å Fab-S. PDB6XCM |
| B38 | Wu, et al.28 | VH3-53 (1) | 9 | VK1-9 (2) | 10 | 117 / NA | ??? | ??? | 1.8 Å Fab-RBD, PDB 7BZ5 |
| CC12.3 | Yuan, et al.30 | VH3-53 (3) | 12 | VK3-20 (1) | 9 | 20 / NA | ??? | ??? | 2.9 Å. Fab-RBD, PDB 6XC7 |
| Class 2: Blocks ACE2, accessibility of RBD epitope in “up”/“down” conformations | |||||||||
| C002 | this study | VH3-30 (1) | 17 | VK1-39 (1) | 9 | 8.9 / 37.6 | Yes | Yes | 3.4 Å Fab-S |
| C104 | this study | VH4-34 (6) | 17 | VK3-20 (3) | 9 | 23.3 / 140 | Yes | Yes | 3.7 Å Fab-S |
| C119 | this study | VH1-46 (1) | 20 | VL2-14 (3) | 11 | 9.1 / 97.8 | Yes | Yes | 3.5 Å Fab-S |
| C121 | this study | VH1-2 (2) | 22 | VL2-23 (0) | 10 | 6.7 / 22.3 | Yes | Yes | 3.6 Å Fab-S |
| C144 | this study | VH3-53 (3) | 25 | VL2-14 (1) | 10 | 6.9 / 29.7 | Yes | Yes | 3.3 Å Fab-S |
| COVA2-39 | Wu, et al.38 | VH3-53 (3) | 17 | VL2-23 (1) | 10 | 36 / NA | ??? | ??? | 1.7 Å Fab-RBD, PDB7JMP |
| 5A6 | Wang, et al.41 | 75.5 / NA | Yes | Yes | 2.4 Å Fab-S | ||||
| P2B-2F6 | Ju, et al.27 | VH4-38*02 (2) | 20 | VL2-8 (0) | 10 | 50 / NA | ??? | ??? | 2.9 Å Fab-RBD, PDB 7BWJ |
| Ab2-4 | Liu, et al.10 | VH1-2 (3) | 15 | VL2-8 (0) | 10 | 394 / NA | Yes | No | 3.2 Å Fab-S, PDB 6XEY |
| BD23 | Cao, et al.13 | VH7-4*02 (0) | 19 | VK1-5*03 (0) | 9 | 4800 / NA | No | No | 3.8 Å Fab-S, PDB 7BYR |
| Class 3: Does not overlap with ACE2 binding site, accessibility of RBD epitope in “up”/“down” conformations | |||||||||
| C135 | this study | VH3-30 (4) | 12 | VK1-5 (3) | 9 | 16.6 / 48.9 | No | No | 3.5 Å Fab-S |
| S309 | Pinto, et al.34 | VH1-18 (6) | 20 | VK3-20 (3) | 8 | 79* / NA | No | No | 3.1 Å Fab-S, PDB6WPS |
| C110 | this study | VH5-51 (2) | 21 | VK1-5 (3) | 9 | 18.4 / 77.3 | No | No | 3.8 Å Fab-S |
| REGN10987 | Hansen, et al.6 | VH3-30 (4) | 13 | VL2-14 (6) | 10 | 6.1 / NA | ??? | ??? | 3.9 Å Fab-RBD, PDB 6XDG |
| Class 4: Does not overlap with ACE2 binding site, accessibility of RBD epitope only in “up” conformation | |||||||||
| CR3022 | Yuan, et al.9 | VH5-51 (8) | 12 | VK4-1 (3) | 9 | >10,000 / NA | ??? | ??? | 3.1 Å Fab-RBD, PDB6W41 |
| COV1-16 | Liu, et al.69 | VH1-46 (1) | 20 | VK1-33 (3) | 10 | 130 / NA | ??? | ??? | 2.9 Å Fab-RBD |
| EY6A | Zhou, et al.70 | VH3-30*18 (3) | 14 | VK1-39 (0) | 10 | 70-20,000** / NA | No | Yes | 3.7 Å Fab-S, PDB6ZDH |
| S304 | Pinto, et al.34 | VH3-13 (5) | 14 | VK1-39 (6) | 10 | >5,000 / NA | No | Yes | 4.3 Å Fab-S, PDB 7JW0 |
| S2A4 | Piccoli, et al.71 | VH3-7 (2) | ? | VL2-23 (0) | ? | 3,500 / NA | No | Yes | 3.3 Å Fab-S, PDB7JVC |
Average human antibody CDRH3 and CDRL3 lengths are 15 (CDRH3) and 9-10 (CDRL3) amino acids.
IC50 calculated against authentic SARS-CoV-2 virus.
IC50 varied depending on neutralization assay utilized.
Unknown IC90s indicated as NA (not available).
Potential for intra-spike crosslinking by an IgG binding to a single spike trimer was evaluated as described in the Methods.
? Sequence information not available.
??? Inference that cannot be made from a structure of a Fab bound to a RBD.
IGHV = Immunoglobulin heavy chain variable gene segment;
IGLV= Immunoglobulin light chain variable gene segment
V gene segments, somatic hypermutation (SHM) information, CDR lengths, IC50/IC90 values for NAbs in this study are from ref.32.