Table 3.
ELISA titer cut-points across different lps-specific immune parameters associated with 70–80% protection from consensus shigellosis post-challenge.
| Immune Parameter | Titer Cut-Pointa | Shigellosis Outcome (n) |
Relative Riskb (P-Value)c | % Efficacyd (P-Value)e | ROC AUCf | SENSg | SPECh | PPVi | NPVj | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| With | Without | Total | |||||||||
| Serum IgG | |||||||||||
| Day 28 Titer | ≥25,600 | 2 | 12 | 14 | 0.254 | 75.6% | 0.805 | 63.2% | 81.8% | 85.7% | 56.3% |
| <25,600 | 9 | 7 | 16 | (0.026) | (0.009) | ||||||
| Day 56 Titer | ≥25,600 | 3 | 12 | 15 | 0.375 | 65.9% | 0.792 | 63.2% | 72.7% | 80.0% | 53.3% |
| <25,600 | 8 | 7 | 15 | (0.128) | (0.025) | ||||||
| Max Titer | ≥51,200 | 1 | 9 | 10 | 0.200 | 82.9% | 0.755 | 47.4% | 90.9% | 90.0% | 50.0% |
| <51,200 | 10 | 10 | 20 | (0.049) | (0.011) | ||||||
| Peak Fold Rise | ≥16 | 3 | 14 | 17 | 0.287 | 69.9% | 0.842 | 73.7% | 72.7% | 82.4% | 61.5% |
| <16 | 8 | 5 | 13 | (0.023) | (0.013) | ||||||
| Serum IgA | |||||||||||
| Day 28 Titer | ≥3200 | 3 | 13 | 16 | 0.328 | 68.0% | 0.718 | 68.4% | 72.7% | 81.3% | 57.1% |
| <3200 | 8 | 6 | 14 | (0.057) | (0.013) | ||||||
| Day 56 Titer | ≥3200 | 2 | 10 | 12 | 0.333 | 71.6% | 0.726 | 52.6% | 81.8% | 83.3% | 50.0% |
| <3200 | 9 | 9 | 18 | (0.121) | (0.019) | ||||||
| Max Titer | ≥3200 | 3 | 15 | 18 | 0.250 | 71.6% | 0.752 | 78.9% | 72.7% | 83.3% | 66.7% |
| <3200 | 8 | 4 | 12 | (0.009) | (0.006) | ||||||
| Peak Fold Rise | ≥16 | 4 | 15 | 19 | 0.331 | 64.1% | 0.674 | 78.9% | 63.6% | 78.9% | 63.6% |
| <16 | 7 | 4 | 11 | (0.047) | (0.017) | ||||||
| Serum IgG1 | |||||||||||
| Day 28 Titer | ≥100 | 1 | 11 | 12 | 0.150 | 85.8% | 0.742 | 57.9% | 90.9% | 91.7% | 55.6% |
| <100 | 10 | 8 | 18 | (0.018) | (0.005) | ||||||
| Day 56 Titer | ≥200 | 1 | 10 | 11 | 0.173 | 84.5% | 0.761 | 52.6% | 90.9% | 90.9% | 52.6% |
| <200 | 10 | 9 | 19 | (0.023) | (0.011) | ||||||
| Max Titer | ≥200 | 1 | 12 | 13 | 0.131 | 86.9% | 0.804 | 63.2% | 90.9% | 92.3% | 58.8% |
| <200 | 10 | 7 | 17 | (0.007) | (0.002) | ||||||
| Peak Fold Rise | ≥4 | 1 | 11 | 12 | 0.150 | 85.8% | 0.796 | 57.9% | 90.9% | 91.7% | 55.6% |
| <4 | 10 | 8 | 18 | (0.018) | (0.005) | ||||||
| Serum IgG2 | |||||||||||
| Day 28 Titer | ≥1600 | 3 | 9 | 12 | 0.563 | 57.4% | 0.691 | 47.4% | 72.7% | 75.0% | 44.4% |
| <1600 | 8 | 10 | 18 | (0.442) | (0.085) | ||||||
| Day 56 Titer | ≥3200 | 1 | 6 | 7 | 0.329 | 75.6% | 0.699 | 31.6% | 90.9% | 85.7% | 43.5% |
| <3200 | 10 | 13 | 23 | (0.215) | (0.088) | ||||||
| Max Titer | ≥3200 | 1 | 6 | 7 | 0.329 | 75.6% | 0.711 | 31.6% | 90.9% | 85.7% | 43.5% |
| <3200 | 10 | 13 | 23 | (0.215) | (0.088) | ||||||
| Peak Fold Rise | ≥8 | 2 | 14 | 16 | 0.194 | 78.7% | 0.803 | 73.7% | 81.8% | 87.5% | 64.3% |
| <8 | 9 | 5 | 14 | (0.007) | (0.004) | ||||||
| Day 28 Titer | ≥13,806 | 4 | 11 | 15 | 0.571 | 54.5% | 0.641 | 57.9% | 63.6% | 73.3% | 46.7% |
| <13,806 | 7 | 8 | 15 | (0.450) | (0.060) | ||||||
| Day 56 Titer | ≥13,933 | 1 | 7 | 8 | 0.275 | 78.7% | 0.780 | 36.8% | 90.9% | 87.5% | 45.5% |
| <13,933 | 10 | 12 | 22 | (0.199) | (0.042) | ||||||
| Max Titer | ≥15,814 | 1 | 7 | 8 | 0.275 | 78.7% | 0.708 | 36.8% | 90.9% | 87.5% | 45.5% |
| <15,814 | 10 | 12 | 22 | (0.199) | (0.021) | ||||||
| Peak Fold Rise | ≥15 | 2 | 9 | 11 | 0.384 | 69.0% | 0.763 | 47.4% | 81.8% | 81.8% | 47.4% |
| <15 | 9 | 10 | 19 | (0.140) | (0.034) | ||||||
| α4β7+ IgG | ≥4 | 1 | 11 | 12 | 0.146 | 85.8% | 0.882 | 64.7% | 88.9% | 91.7% | 57.1% |
| <4 | 8 | 6 | 14 | (0.014) | (0.005) | ||||||
| α4β7- IgG | ≥2 | 3 | 15 | 18 | 0.222 | 71.6% | 0.797 | 88.2% | 66.7% | 83.3% | 75.0% |
| <2 | 6 | 2 | 8 | (0.008) | (0.006) | ||||||
| α4β7+ IgA | ≥8 | 1 | 7 | 8 | 0.281 | 78.7% | 0.696 | 41.2% | 88.9% | 87.5% | 44.4% |
| <8 | 8 | 10 | 18 | (0.190) | (0.042) | ||||||
| α4β7- IgA | ≥4 | 1 | 6 | 7 | 0.339 | 75.6% | 0.647 | 35.3% | 88.9% | 85.7% | 42.1% |
| <4 | 8 | 11 | 19 | (0.357) | (0.088) | ||||||
| IgG | ≥64 | 1 | 8 | 9 | 0.233 | 81.0% | 0.729 | 42.1% | 90.9% | 88.9% | 47.6% |
| <64 | 10 | 11 | 21 | (0.100) | (0.021) | ||||||
| IgA | ≥64 | 7 | 15 | 22 | 0.636 | 45.7% | 0.590 | 78.9% | 36.4% | 68.2% | 50.0% |
| <64 | 4 | 4 | 8 | (0.417) | (0.089) | ||||||
ELISA titer cut-point chosen based on the titer that provided as close to or between 70 and 80% efficacy.
Calculated as: (shigellosis rate among vaccinees at or above cut-point / shigellosis rate among vaccinees below cut-point).
P-value determined by Fisher's Exact Test comparing shigellosis rate among vaccinees at or above cut-point versus shigellosis rate among vaccinees below cut-point.
Calculated as: [1 – (shigellosis rate among vaccinees at or above cut-point / shigellosis rate among placebo recipients)] x 100.
P-value determined by Fisher's Exact Test comparing shigellosis rate among vaccinees at or above cut-point versus shigellosis rate among placebo recipients.
Area under the curve (AUC) of a receiver operator characteristic (ROC) graph.
Sensitivity = (number of subjects without shigellosis at or above the cut-point / total number of subjects without shigellosis).
Specificity = (number of subjects with shigellosis at or above the cut-point / total number of subjects with shigellosis).
Positive Predictive Value = (number of subjects without shigellosis at or above the cut-point / total number of subjects at or above the cut-point).
Negative Predictive Value = (number of subjects with shigellosis below the cut-point / total number of subjects below the cut-point).