Table 2.
Broadly neutralizing antibodies and their characteristics
| HIV-1 epitope | bnAb | Breadth (%)a (potency (μg ml–1)b) | VH/VL gene | HCDR3 length | LCDR3 length | VH mutation frequency (%) | VL mutation frequency (%) | Germline-targeting priming immunogen |
|---|---|---|---|---|---|---|---|---|
| CD4 binding site | N49P7 | 100 (0.10) | VH1–2/VL2–11 | 19 | 5 | 24.5 | 14.1 | NA |
| N6 | 99 (0.062) | VH1–2/VK1–33 | 13 | 5 | 30.2 | 22.4 | ||
| 12A12 | 93 (0.221) | VH1–2/VK1–33 | 13 | 5 | 21.9 | 15.5 | eOD-GT8 (ref.77) | |
| VRC01 | 91 (0.377) | VH1–2/VK3–20 | 12 | 5 | 31.6 | 17.2 | 426c.TM4ΔV1-3 (ref.110), BG505 SOSIP 4.1 GT1 (ref.53), eOD-GT8 | |
| 3BNC117 | 89 (0.116) | VH1–2/VK1–33 | 10 | 5 | 23.7 | 14.8 | eOD-GT8 | |
| VRC-CH31 | 84 (0.321) | VH1–2/VK1–33 | 13 | 5 | 20.2 | 15.2 | 426c.TM4ΔV1-3, eOD-GT8 | |
| PCIN63.71I | 84 (0.46) | VH1–2/VK1–6 | 13 | 5 | 14.6 | 12.5 | ||
| VRC-PG04 | 81 (0.317) | VH1–2/VK3–40 | 14 | 5 | 28.6 | 15.2 | eOD-GT8 | |
| VRC-PG20 | 80 (0.226) | VH1–2/VL2–14 | 13 | 5 | 24.0 | 14.8 | 426c.TM4ΔV1-3, eOD-GT8 | |
| IOMA | 49 (2.33) | VH1–2/VL2–23 | 15 | 8 | 25.4 | 23.3 | ||
| 1-18 | 97 (0.048) | VH1–46/VK3–20 | 16 | 9 | 26.4 | 20.2 | ||
| CH235.12 | 89 (0.70) | VH1–46/VK3–15 | 13 | 8 | 25.0 | 14.8 | CH505.M5.G458Y.GNTI- (ref.120) | |
| 1B2530 | 72 (3.62) | VH1–46/VL1–47 | 16 | 11 | 27.8 | 15.7 | ||
| 8ANC131 | 71 (1.78) | VH1–46/VK3–20 | 16 | 9 | 25.7 | 17.2 | ||
| CH103 | 67 (2.28) | VH4–59/VL3–1 | 13 | 10 | 16.9 | 11.1 | CH505 T/F33 | |
| V3 glycan | PGT128 | 68 (0.064) | VH4–39/VL2–8 | 19 | 10 | 19.1 | 7.0 | |
| PGT121 | 66 (0.072) | VH4–59/VL3–21 | 24 | 12 | 19.6 | 16.5 | MD39-11MUTb (ref.126), RC1-4Fill (ref.129) | |
| BG18 | 61 (0.032) | VH4–4/VL3–25 | 21 | 11 | 21.5 | 17.6 | MD39-11MUTb, N332 GT5 (ref.51) | |
| BF520.1 | 53c (7.31) | VH1–2/VK3–15 | 18 | 11 | 6.6 | 5.3 | ||
| PGDM12 | 54 (0.14) | VH3–11/VK2–24 | 19 | 9 | 19.1 | 14.3 | ||
| DH270.6 | 51 (0.21) | VH1–2/VL2–23 | 18 | 10 | 12.8 | 6.7 | CH848 SOSIP 10.17 DT (ref.76) | |
| PCDN76-33A | 46 (0.50) | VH4–34/VK3–20 | 20 | 8 | 13.0 | 11.6 | ||
| V2 apex | PG9 | 87 (0.154) | VH3–33/VL2–14 | 28 | 10 | 12.6 | 6.3 | BG505 SOSIP 4.1 GT1, BG505 SOSIP 4.1 GT1.1 (ref.228), ZM233 (ref.132), KER2018 (ref.133), BB201.B42 (ref.133) |
| PGDM1400 | 83 (0.02) | VH1–8/VK2–28 | 32 | 9 | 26.4 | 11.8 | ||
| VRC26.25 | 70 (0.004) | VH3–30/VL1–51 | 36 | 12 | 12.2 | 8.6 | ||
| CH01 | 54 (1.38) | VH3–20/VK3–20 | 24 | 9 | 16.7 | 11.2 | BG505 SOSIP 4.1 GT1, BG505 SOSIP 4.1 GT1.1, ZM233, CM244 (ref.132), Q23.17 (ref.132), WITO132, T250 (ref.131) | |
| PCT64-35Md | 35 (0.41) | VH3–15/VK3–20 | 23 | 8 | 11.2 | 4.9 | ||
| MPER | 10E8 | 98 (0.356) | VH3–15/VL3–19 | 20 | 12 | 21.4 | 13.4 | NA |
| DH511.2 | 98 (0.943) | VH3–15/VK1–39 | 21 | 11 | 19.8 | 14.0 | ||
| 4E10 | 98 (1.81) | VH1–69/VK3–20 | 18 | 9 | 6.9 | 4.1 | ||
| VRC42.1 | 96 (4.09) | VH1–69/VK3–20 | 15 | 9 | 10.8 | 5.6 | ||
| VRC43.1 | 63 (1.34) | VH4–4/VL7–43 | 19 | 9 | 11.1 | 8.5 | ||
| PGZL1 | 84 (6.06) | VH1–69/VK3–20 | 15 | 9 | 20.9 | 11.8 | ||
| 2F5 | 58 (2.83) | VH2–5/VK1–13 | 22 | 9 | 13.1 | 11.0 | MPER liposome87 | |
| Fusion peptide | PGT151 | 73 (0.04) | VH3-30/VK2D–20 | 26 | 9 | 20.8 | 11.5 | NA |
| VRC34 | 47 (0.32) | VH1–2/VK1–9 | 13 | 9 | 14.9 | 8.7 | ||
| Silent face | SF12 | 62 (0.20) | VH4–59/VK3-20 | 21 | 6 | 16.3 | 13.9 | NA |
| Fab dimer glycan | 2G12e | 21 (3.75) | VH3–21/VK1–5 | 14 | 9 | 21.1 | 11.7 | V3-glycopeptide156 |
The following bnAbs met the inclusion criteria but were not included for space considerations: 3BNC55, VRC13, VRC16, VRC18, VRC27. Adapted with permission from ref.227. bnAb, broadly neutralizing antibody; MPER, membrane proximal external region; NA, not available; VH1–2, variable heavy 1–2; HCDR3, heavy chain complementarity determining region 3; LCDR3, light chain complementarity determining region 3. aOnly bnAbs that have >45% breadth on a multiclade panel of >50 viruses (from CATNAP database229), except where noted. bGeometric mean of detected. cBF520.1 neutralization was only tested on 15 viruses but is included here because it notably was induced in an infant38. dPCT64 included because it is only one of two V2 lineages profiled from acute HIV-1 infection to bnAb breadth. e2G12 does not meet >45% breadth threshold but is included because expected high precursor frequency of natural Fab-dimerized glycan (FDG) antibodies makes this class an attractive target for design.