Table 3. HLA Allelic Associations with VACV-Specific Immune Responses in the Discovery and Replication Study Cohorts.
| Discovery Cohort (Dryvax vaccine) | Replication Cohort (ACAM2000 vaccine) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Immune Measure |
HLA locus | Allele | Allele counts |
Median | 25th Percentile |
75th Percentile |
Allele p-value |
Global p- value |
Allele counts |
Median | 25th Percentile |
75th Percentile |
Allele p-value |
Global p- value |
| Neutralizing Antibody (ID50) | Overall | 2142 | 132.6 | 78.8 | 206.5 | 1053 | 113.5 | 63.0 | 190.4 | |||||
| HLA-B | *40:02 | 47 | 108.1 | 66.5 | 191.4 | 0.119 | 0.044 | 42 | 91.5 | 55.8 | 169.6 | 0.021 | 0.056 | |
| HLA-DQB1 | *03:01 | 417 | 124.6 | 74.8 | 194.5 | 0.119 | 0.041 | 356 | 105.0 | 59.4 | 184.4 | 0.160 | 0.007 | |
| *03:02 | 206 | 152.0 | 100.1 | 228.3 | 0.015 | 238 | 134.4 | 74.3 | 206.7 | 0.010 | ||||
| *06:04 | 70 | 151.4 | 96.9 | 247.0 | 0.017 | 68 | 126.4 | 67.3 | 204.8 | 0.166 | ||||
| *06:09 | 28 | 147.7 | 94.4 | 296.5 | 0.148 | 31 | 169.7 | 110.2 | 226.6 | 0.001 | ||||
| Total PBMC IFN-γ ELISPOT (SFC 2 × 105 cells) | Overall | 2116 | 52.0 | 24 .0 | 88.0 | 1048 | 17.0 | 5.0 | 37.0 | |||||
| HLA-DRB1 | *04:03 | 22 | 38.5 | 22.0 | 108.0 | 0.094 | 0.052 | 18 | 12.0 | 1.0 | 33.0 | 0.047 | 0.587 | |
| *08:01 | 26 | 60.5 | 29.0 | 105.0 | 0.085 | 43 | 20.0 | 11.0 | 40.0 | 0.056 | ||||
| *15:01 | 192 | 50.0 | 25.0 | 83.0 | 0.016 | 227 | 18.0 | 4.0 | 36.0 | 0.007 | ||||
| IFN-γ (pg/mL) | Overall | 2076 | 289.5 | 11.7 | 1261.2 | 1039 | 273.6 | 33.0 | 934.7 | |||||
| HLA-DQB1 | *06:02 | 261 | 245.8 | 0.0 | 1299.0 | 0.173 | 0.055 | 254 | 226.4 | 18.0 | 822.2 | 0.167 | 0.669 | |
| HLA-DRB1 | *15:01 | 190 | 181.7 | -18.2 | 1086.7 | 0.052 | 0.019 | 224 | 203.0 | 2.9 | 822.2 | 0.014 | 0.565 | |
| IL12p40 (pg/mL) | Overall | 1786 | 62.4 | 29.5 | 122.4 | 1041 | 94.2 | 33.3 | 218.8 | |||||
| HLA-A | A*34:02 | 14 | 35.5 | 8.1 | 108.1 | 0.028 | 0.042 | 11 | 205.7 | 104.1 | 509.6 | 0.045 | 0.163 | |
NOTE. Analyses adjusted for time from immunization to blood draw, gender, race, and age at smallpox vaccination. HLA alleles with p-values < 0.10 are bolded. The direction of association for the shaded alleles was in the opposite direction between the two cohorts.