TABLE 2.
Antibody and inhibitor relative IC50s by the TZM-bl and A3R5 assaysa
Env variant and antibody or inhibitor | TZM-bl assay |
A3R5 assay |
||||||
---|---|---|---|---|---|---|---|---|
Increased neutralization resistance of virus | P value | Relative IC50 (antibody, μg/ml; inhibitor, nM) |
Increased neutralization resistance of virus | P value | Relative IC50 (antibody, μg/ml; inhibitor, nM) |
|||
CA | CF | CA | CF | |||||
Antibodies | ||||||||
BAL | ||||||||
huOKT4A | CF | 0.08 | 0.042 | 0.064 | ||||
hu5A8 | — | — | — | — | — | — | — | — |
4E10 | — | — | — | — | CA | 1 | 3.10 | 3.06 |
10E8 | CF | 0.3 | 1.54 | 2.78 | CF | 0.6 | 1.23 | 1.62 |
VRC01 | CA | 0.0001 | 0.22 | 0.071 | CA | 0.0001 | 0.22 | 0.055 |
CH01 | — | — | — | — | — | — | — | — |
PGT126 | CA | 0.0001 | 0.8 | 0.053 | CA | 0.004 | 0.18 | 0.072 |
PG9 | — | — | — | — | — | — | — | — |
WITO | ||||||||
huOKT4A | CF | 0.8 | 0.074 | 0.074 | ||||
hu5A8 | CA | 0.0008 | 0.29 | 0.080 | CA | 0.0001 | 0.016 | 0.0011 |
4E10 | — | — | — | — | CA | 1 | 3.74 | 2.69 |
10E8 | CA | 1 | 3.44 | 3.09 | CA | 0.5 | 1.67 | 0.77 |
VRC01 | CA | 0.0001 | 7.44 | 1.45 | CA | 0.0001 | 1.30 | 0.13 |
CH01 | — | — | — | — | CA | 0.002 | 1.09 | 0.13 |
PGT126 | — | — | — | — | CA | 0.3 | 3.16 | 2.03 |
PG9 | CA | 0.0001 | 0.22 | 0.0070 | CA | 0.0001 | 0.071 | 0.0047 |
CH040 | ||||||||
huOKT4A | CF | 0.8 | 0.082 | 0.10 | ||||
hu5A8 | CF | 1 | 0.21 | 0.21 | CA | 0.0001 | 0.024 | 0.0025 |
4E10 | — | — | — | — | — | — | — | — |
10E8 | CF | 1 | 2.57 | 3.37 | CF | 0.6 | 0.82 | 1.86 |
VRC01 | CA | 0.02 | 1.96 | 1.01 | CA | 0.0001 | 3.19 | 0.49 |
CH01 | — | — | — | — | — | — | — | — |
PGT126 | — | — | — | — | — | — | — | — |
PG9 | — | — | — | — | — | — | — | — |
CH077 | ||||||||
huOKT4A | CF | 0.8 | 0.031 | 0.036 | ||||
hu5A8 | CF | 0.5 | 0.078 | 0.13 | CA | 0.009 | 0.012 | 0.0018 |
4E10 | — | — | — | — | CF | 0.3 | 0.62 | 3.36 |
10E8 | CF | 0.4 | 2.22 | 3.19 | CA | 0.2 | 2.29 | 0.82 |
VRC01 | CA | 0.0001 | 3.34 | 1.26 | CA | 0.0001 | 2.23 | 0.27 |
CH01 | — | — | — | — | CA | 0.4 | 1.88 | 0.33 |
PGT126 | CF | 0.5 | 0.088 | 0.049 | CA | 0.0001 | 1.34 | 0.0049 |
PG9 | CA | 0.0001 | 0.059 | 0.013 | CA | 0.0001 | 0.35 | 0.0034 |
Inhibitors | ||||||||
BAL | ||||||||
PMPA | CF | 0.002 | 772 | 2,001 | CF | 0.7 | 1,103 | 1,303 |
Nevirapine | CF | 0.6 | 63.8 | 84.6 | CF | 1 | 53.25 | 54.8 |
T-20 | — | — | — | — | CA | 1 | 93.0 | 85.4 |
TAK-779 | CF | 0.7 | 517 | 807 | CA | 0.7 | 89.1 | 60.3 |
Maraviroc | CA | 0.2 | 15.1 | 6.58 | CF | 0.4 | 1.03 | 4.17 |
WITO | ||||||||
PMPA | CF | 0.6 | 1,181 | 2,021 | CF | 0.7 | 436 | 547.5 |
Nevirapine | CF | 0.7 | 40.3 | 58.4 | CA | 0.4 | 43.5 | 23.5 |
T-20 | — | — | — | — | CF | 1 | 59.8 | 82.2 |
TAK-779 | CF | 0.9 | 134 | 194 | CA | 0.2 | 74.4 | 33.2 |
Maraviroc | CA | 0.3 | 19.4 | 11.4 | CA | 0.0001 | 20.5 | 2.56 |
CH040 | ||||||||
PMPA | CF | 0.08 | 505 | 1,288 | CA | 0.6 | 1,327 | 856 |
Nevirapine | CA | 0.6 | 86.3 | 44.6 | CA | 0.9 | 39.2 | 36.8 |
T-20 | CA | 0.4 | 92.5 | 52.0 | CA | 1 | 91.4 | 72.8 |
TAK-779 | CA | 0.05 | 77.9 | 43.3 | CA | 0.04 | 44.8 | 16.6 |
Maraviroc | CA | 0.009 | 4.44 | 1.12 | CA | 0.0008 | 5.49 | 0.27 |
CH077 | ||||||||
PMPA | CF | 0.5 | 1,080 | 1,661 | CF | 0.1 | 284.5 | 716 |
Nevirapine | CF | 0.7 | 41.6 | 50.9 | CA | 0.9 | 33.6 | 27.1 |
T-20 | CF | 1 | 58.9 | 68.0 | CF | 0.4 | 12.2 | 38.3 |
TAK-779 | CF | 0.0005 | 9.77 | 43.1 | CF | 0.6 | 502 | 690 |
Maraviroc | CF | 0.0001 | 0.088 | 1.60 | CF | 0.5 | 883 | 1,481 |
Antibody and inhibitor relative IC50s against cell-associated (CA) and cell-free (CF) virus are shown for TZM-bl and A3R5 target cells. Values were determined based on the neutralization dose responses from Fig. S2 and S3 in the supplemental material. Significant differences (in bold) between the log IC50s for the cell-associated and cell-free Env variants were assessed with ANOVA following a nonlinear regression analysis with a variable slope equation in GraphPad Prism. Only P values that were significant after Holm's adjustment for multiple comparisons were considered significant. Blank entries represent cases in which an antibody was not used in the A3R5 assay. —, cases in which the IC50 could not be calculated with the four-parameter logistic model.