Table 2.
Performance of approaches 1–4 for predicting ID50 (Panel A) and ID80 (Panel B) neutralization titers broken down by the status (detectable vs. undetectable, + vs. -) of measured serum concentration and serum neutralization titer
| ID50 |
|||||||||
|---|---|---|---|---|---|---|---|---|---|
| Detectable |
|||||||||
| A Virus | IC50 (µg/ml)* | Serum conc.a | Serum neut. Titerb | # of samples | Appr. 1 | Appr. 2 | Appr. 3 | Appr. 4 | Reported Values |
| H704_2544_140eN01 | 1.02 | − | − | 24 | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | Classification accuracy (95% CI)c |
| + | − | 95 | 0.72 (0.62, 0.80) | 0.73 (0.63, 0.81) | 0.74 (0.64, 0.82) | 0.74 (0.64, 0.82) | Classification accuracy (95% CI) | ||
| + | + | 127 | 0.68 (0.48, 0.82) | 0.65 (0.42, 0.80) | 0.77 (0.61, 0.87) | 0.76 (0.6, 0.86) | CCCrmd (95% CI) | ||
| H703_1750_140Es | 0.92 | − | − | 24 | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | Classification accuracy (95% CI) |
| + | − | 94 | 0.66 (0.56, 0.75) | 0.66 (0.56, 0.75) | 0.69 (0.59, 0.77) | 0.68 (0.58, 0.77) | Classification accuracy (95% CI) | ||
| + | + | 128 | 0.70 (0.52, 0.82) | 0.69 (0.48, 0.83) | 0.85 (0.76, 0.91) | 0.85 (0.76, 0.91) | CCCrm (95% CI) | ||
| H703_1471_190s | 0.19 | - | − | 24 | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | Classification accuracy (95% CI) |
| + | − | 9 | NAe | NAe | NAe | NAe | Classification accuracy | ||
| + | + | 213 | 0.80 (0.68, 0.88) | 0.77 (0.63, 0.86) | 0.87 (0.8, 0.92) | 0.85 (0.77, 0.91) | CCCrm (95% CI) | ||
| H704_1535_030sN | 0.12 | − | − | 22 | 1.00 (0.85, 1.00) | 0.86 (0.66, 0.95) | 1.00 (0.85, 1.00) | 0.91 (0.72, 0.98) | Classification accuracy (95% CI) |
| − | + | 2 | NAe | NAe | NAe | NAe | NAe | ||
| + | − | 6 | NAe | NAe | NAe | NAe | NAe | ||
| + | + | 216 | 0.75 (0.61, 0.85) | 0.74 (0.59, 0.84) | 0.86 (0.78, 0.92) | 0.82 (0.71, 0.89) | CCCrm (95% CI) | ||
| Breakthrough virus geometric meanf | 0.38 | − | − | 22 | 1.00 (0.85, 1.00) | 1.00 (0.85, 1.00) | 1.00 (0.85, 1.00) | 1.00 (0.85, 1.00) | Classification accuracy (95% CI) |
| − | + | 2 | NAe | NAe | NAe | NAe | NAe | ||
| + | - | 4 | NAe | NAe | NAe | NAe | NAe | ||
| + | + | 218 | 0.78 (0.65, 0.86) | 0.72 (0.57, 0.82) | 0.85 (0.75, 0.91) | 0.86 (0.77, 0.92) | CCCrm (95% CI) | ||
| PVO.4 | 0.57 | − | − | 24 | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | Classification accuracy (95% CI) |
| + | − | 64 | 0.50 (0.38, 0.62) | 0.52 (0.40, 0.64) | 0.70 (0.58, 0.80) | 0.59 (0.47, 0.70) | Classification accuracy (95% CI) | ||
| + | + | 158 | 0.59 (0.36, 0.76) | 0.57 (0.33, 0.74) | 0.89 0.81, 0.93) | 0.86 (0.78, 0.92) | CCCrm (95% CI) | ||
| CH0505TF.gly4 | 0.002 | − | + | 24 | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 0.96 (0.80, 0.99) | 1.00 (0.86, 1.00) | Classification accuracy (95% CI) |
| |
|
+ |
+ |
222 |
0.62 (0.43, 0.76) |
0.65 (0.47, 0.78) |
0.82 (0.74, 0.88) |
0.74 (0.59, 0.84) |
CCCrm (95% CI) |
| ID80 |
|||||||||
| Detectable |
|||||||||
| B Virus |
IC80 (µg/ml)* |
Serum conc.a |
Serum neut. Titerb |
# of samples |
Appr. 1 |
Appr. 2 |
Appr. 3 |
Appr. 4 |
|
| H704_2544_140eN01 | 2.98 | − | − | 24 | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | Classification accuracy (95% CI) |
| + | − | 156 | 0.88 (0.82, 0.92) | 0.88 (0.82, 0.92) | 0.87 (0.81, 0.91) | 0.91 (0.85, 0.95) | Classification accuracy (95% CI) | ||
| + | + | 66 | 0.80 (0.62, 0.9) | 0.83 (0.69, 0.91) | 0.73 (0.54, 0.85) | 0.81 (0.67, 0.9) | CCCrm (95% CI) | ||
| H703_1750_140Es | 2.64 | − | − | 24 | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | Classification accuracy (95% CI) |
| + | − | 157 | 0.83 (0.76, 0.88) | 0.84 (0.77, 0.89) | 0.85 (0.79, 0.90) | 0.90 (0.84, 0.94) | Classification accuracy (95% CI) | ||
| + | + | 65 | 0.83 (0.67, 0.91) | 0.86 (0.71, 0.94) | 0.78 (0.61, 0.88) | 0.86 (0.74, 0.92) | CCCrm (95% CI) | ||
| H703_1471_190s | 0.57 | − | − | 24 | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | Classification accuracy (95% CI) |
| + | − | 53 | 0.68 (0.55, 0.79) | 0.70 (0.57, 0.81) | 0.91 (0.80, 0.96) | 0.74 (0.61, 0.84) | Classification accuracy (95% CI) | ||
| + | + | 169 | 0.85 | 0.82 | 0.89 | 0.87 | CCCrm (95% CI) | ||
| H704_1535_030sN | 0.33 | − | − | 24 | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | Classification accuracy (95% CI) |
| + | - | 34 | 0.38 (0.24, 0.55) | 0.38 (0.24, 0.55) | 0.74 (0.57, 0.86) | 0.44 (0.29, 0.60) | Classification accuracy (95% CI) | ||
| + | + | 188 | 0.81 (0.69, 0.89) | 0.78 (0.65, 0.87) | 0.87 (0.8, 0.92) | 0.84 (0.75, 0.9) | CCCrm (95% CI) | ||
| Breakthrough virus geometric meanf | 1.10 | − | − | 24 | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | Classification accuracy (95% CI) |
| + | − | 34 | 1.00 (0.90, 1.00) | 1.00 (0.90, 1.00) | 1.00 (0.90, 1.00) | 0.97 (0.85, 0.99) | Classification accuracy (95% CI) | ||
| + | + | 188 | 0.70 (0.57, 0.8) | 0.63 (0.48, 0.75) | 0.83 (0.71, 0.91) | 0.85 (0.74, 0.92) | CCCrm (95% CI) | ||
| PVO.4 | 1.74 | − | − | 24 | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | Classification accuracy (95% CI) |
| + | − | 122 | 0.77 (0.69, 0.84) | 0.75 (0.67, 0.82) | 0.75 (0.67, 0.82) | 0.82 (0.74, 0.88) | Classification accuracy (95% CI) | ||
| + | + | 100 | 0.68 (0.46, 0.82) | 0.71 (0.51, 0.84) | 0.88 (0.79, 0.93) | 0.90 (0.83, 0.94) | CCCrm (95% CI) | ||
| CH0505TF.gly4 | 0.005 | − | − | 1 | NAe | NAe | NAe | NAe | NAe |
| − | + | 23 | 1.00 (0.86, 1.00) | 1.00 (0.86, 1.00) | 0.96 (0.80, 0.99) | 1.00 (0.86, 1.00) | Classification accuracy (95% CI) | ||
| + | + | 222 | 0.84 (0.71, 0.91) | 0.87 (0.77, 0.92) | 0.89 (0.83, 0.93) | 0.86 (0.78, 0.92) | CCCrm (95% CI) | ||
*IC50 and IC80 values are for the clinical lot of VRC01, calculated as the geometric mean of all replicates.
aDetectable serum concentration (+) = Serum concentration > 1.0 µg/mL;
No detectable serum concentration (-) = Serum concentration ≤ 1.0 µg/mL.
bDetectable serum neutralization titer (+) = Serum neutralization titer > 10;
No detectable serum neutralization titer (-) = Serum neutralization titer ≤ 10.
cClassification accuracy = percent of samples correctly predicted to have neutralization titer > 10 or ≤ 10 for samples with empirically measured neutralization titer > 10 or ≤ 10, respectively.
dCCCrm = Concordance Correlation Coefficient for repeated measurements, expressing how well the predicted and measured neutralization titers agree with each other. Only calculated for samples with detectable VRC01 serum concentration and VRC01 serum neutralization titer.
eNA = Not applicable. Results are only shown in a row if n ≥ 10.
Appr. = Approach.
fGeometric mean: predict the geometric mean titers based on the geometric mean of the observed titers across the 4 breakthrough viruses, and the geometric mean of the IC50 values (Panel A) or of the IC80 values (Panel B) of the 4 breakthrough viruses (as if the geometric mean corresponded to a single virus).