TABLE 3.
N36Mut(e,g) and Fab bF-3674 neutralize contemporary primary isolates of subtype B and C clades of HIV-1 synergisticallya
| Pseudovirus | bF-3674/N36Mut(e,g) combination ratio | IC50 in combination (mean ± SD)
|
Individual IC50 (mean ± SD)
|
DRI (mean ± SD)
|
CI (mean ± SD) | |||
|---|---|---|---|---|---|---|---|---|
| bF-3674 (nM) | N36Mut(e,g) (μM) | bF-3674 (nM) | N36Mut(e,g) (μM) | bF-3674 | N36Mut(e,g) | |||
| B.CAAN5342.A2 | 1:20 | 72 ± 7 | 1.4 ± 0.1 | 310 ± 60 | 41 ± 7 | 4.3 ± 1.0 | 28 ± 5 | 0.3 ± 0.1 |
| 1:40 | 59 ± 4 | 2.4 ± 0.1 | 5.3 ± 1.1 | 17 ± 3 | 0.3 ± 0.1 | |||
| B.6535.3 | 1:20 | 120 ± 17 | 2.5 ± 0.3 | 2840 ± 820 | 7.1 ± 1.1 | 24 ± 8 | 2.9 ± 0.6 | 0.4 ± 0.2 |
| 1:40 | 70 ± 12 | 2.8 ± 0.5 | 41 ± 14 | 2.6 ± 0.6 | 0.4 ± 0.2 | |||
| B.PVO.4 | 1:20 | 730 ± 210 | 15 ± 4 | NAb | 59 ± 17 | 4.0 ± 1.6 | —c | |
| 1:40 | 280 ± 70 | 11 ± 3 | 5.3 ± 2.0 | —c | ||||
| C.ZM233M.PB6 | 1:20 | 12 ± 1 | 0.2 ± 0.0 | 44 ± 10 | 11 ± 4 | 3.8 ± 0.9 | 46 ± 17 | 0.3 ± 0.2 |
| 1:40 | 9 ± 2 | 0.4 ± 0.1 | 5.2 ± 1.5 | 31 ± 13 | 0.2 ± 0.1 | |||
| C.DU172.17 | 1:20 | 27 ± 4 | 0.6 ± 0.1 | 70 ± 13 | 4.6 ± 1.0 | 2.6 ± 0.7 | 8.4 ± 2.3 | 0.6 ± 0.2 |
| 1:40 | 18 ± 3 | 0.7 ± 0.1 | 4.0 ± 1.0 | 6.4 ± 1.7 | 0.5 ± 0.2 | |||
a
Envelope clones from standard reference panel B (B.CAAN5342.A2, B.6535.3, and B.PVO.4) (30) and C (C.ZM233M.PB6 and C.DU172.17) (34) were used to produce the Env-pseudotyped HIV-1.
b
NA, no detectable neutralizing activity in the range of concentrations tested [up to 1 μM for bF-3674 and 20 μM for N36Mut(e,g)].
c
A combination index could not be obtained since Fab-3674 displayed no detectable neutralizing activity on its own (see footnote b).