Table 1.
Characteristics of broadly neutralizing antibody lineages that have been the subject of Env/antibody coevolution studies
| Epitope | Characteristics of bNAbs |
Donor | Sampling | Ab lineage |
Breadth median IC50 |
VH-gene SHM (nt) |
VL-gene | CDR3 length |
indels | Poly- auto- reactivity |
Lineage emergence |
Breadth in lineage |
Serum breadth |
Viral subtype |
Viral sequencing |
UCA binds/ neutralizes T/F |
Escape | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CD4bs | Multiple classes:-VH-generestricted: conserved angle of approach * VRC01-class: VH1-2, 5aa CRDL3, flexible/short CDRL1 loop *VH1-46 restricted - CDRH3 binder: Various angles of approach, gene usage and structural characteristics Highly somatically mutated (mean 28.4%] Need to accomodate surrounding glycans (N276 in loopD, N462 in V5-loop] | CH505 | 4–160 wpi | CH103 | 55% 4.54 μg/ml | VH4-59 14% | VL3-1 | H: 15 aa L: 10 aa | Yes Del CDRL1 | ++ | 14 wpi | 144 wpi | 84 wpi | C | Yes | Neutralization | LoopD V5 loop CD4bs loop | [24-25] |
| CH505 | 4–323 wpi | CH235 | 90% 0.6 μg/ml | VH1-46 28% | VK3-15 | H: 15 aa L: 8 aa | No | ++ | 14 wpi | 152 wpi | 84 wpi | C | Yes | Weak binding | LoopD V5 loop CD4bs loop | [23,24] | ||
| PC063 | 7–322 wpi | PCIN63 | 80% 0.24 μg/ml | VH1-2 15% | VK1-5 | H: 15 aa L: 5 aa | No | Variable | 168 wpi | 289 wpi | 266 wpi | C | Yes | No binding | LoopD V5 loop CD4bs loop | [26■■] | ||
| V2-glycan | Long (25–39aa) anionic CDHR3 Majority VH3 + DH3 genes Limited angles of approach Glycan binding (N160, N156) V2 C-strand K/R residues (166, 169, 171] | CAP256 | 24–206 wpi | VRC26-CAP256 | 63% 0.003 μg/ml | VH3-30 12% | VL1-51 | H: 36 aa L: 13 aa | No | - | 38 wpi | 119 wpi | 84 wpi | C | Yes | Neutralization | 166 and 169 | [11,28,30] |
| PC064 | 14–200 wpi | PCT64 | 37% 0.42 μg/ml | VH3-15 13% | VK3-20 | H: 25aa L: 8 aa | No | +/− | 43 wpi | 80 wpi | 80 wpi | A | Yes | Binding to 293S-expressed Env | 166 and 169 | [34■■,35■■] | ||
| V3-glycan | Diverse gene families Frequent indels Diverse angles of approach N332-glycan + GDIR dependant V3-glycans promiscuity | PC076 | 23–192 wpi | PCDN | 47% 0.53 μg/ml | VH4-34 16% | VK3-20 | H: 22 aa L: 8aa | No | +/− | 72 wpi | 120 wpi | 120 wpi | C | Yes | No binding | N328, N332 | [41] |
| PC039 | 15–265 wpi | PCN39 | 45% 0.03 μg/ml | VH4-34 16% | VK3-20 | H: 22 aa L: 10aa | Yes Ins CDRH1 | ++ | 37 wpi | 72 wpi | 84 wpi | C | Yes | No binding | 2 pathways–GDIR, 301, 332–V3 deletion | Landais, Poignard, Murrell, Wilson et al., unpublished | ||
| BF520 | 14–26 wpi | BF520.1 | 58% 1.95 μg/ml | VH1-2 7% | VK3-15 | H: 20 aa L: 7aa | No | 26 wpi | 62 wpi | 62 wpi | A | Yes | No autologous Env binding but binds BG505-SOSIP | [39,43■■] | ||||
| CH848 | 11–246 wpi | DH270 | 55% 0.08 μg/ml | VH1-2 13% | VL2-23 | H: 20aa L: 9 aa | No | +/− | 186 wpi | 205 wpi | n.a. | C | Yes | Weak binding to V3-peptide mimic | V1-loop GDIR N332 > N334 | [42■■] | ||
| MPER | Auto/poly-reactivity Narrow angle of approach Bind viral membrane | RV217-40512 | 4–163 wpi | RV217-VRC42 | 96% 4.7 μg/ml | VH1-69 11% | VK3-20 | H: 15 aa L: 9 aa | No | + | 22 wpi | 69 wpi | AE | Yes | Binding to scaffolded MPER peptide on 60-mer | [44■■] | ||
| RV217-40512 | 4–163 wpi | RV217-VRC43 | 65% 1.7 μg/ml | VH4-4 11% | VL7-23 | H: 19 aa L: 9 aa | No | +/− | 22 wpi | 69 wpi | AE | Yes | [44■■] | |||||
| RV217-40512 | 4–163 wpi | RV217-VRC46 | 30% 11 μg/ml | VH1-69 9% | VK1-39 | H: 14 aa L: 9 aa | No | ++ | 22 wpi | 69 wpi | AE | Yes | [44■■] |