Human leukocyte antigen genotypes in the genetic control of adaptive immune responses to smallpox vaccine.

BACKGROUND

The role of human leukocyte antigen (HLA) genes in mediating adaptive immune responses to smallpox vaccine remains unknown.

METHODS

We determined genotypes for a group of individuals (n = 1071) who received a single dose of smallpox vaccine (Dryvax, Wyeth Laboratories) and examined associations between HLA alleles and 15 immune outcomes to smallpox vaccine on a per-locus and a per-allele level.

RESULTS

We found significant associations between the HLA-B and HLA - DQB1 loci and vaccinia-induced antibodies (P = .04 for each locus), with the HLA-B1302 (P = .036), B3802 (P = .011), DQB10302 (P = .015), and DQB10604 (P = .017) alleles being associated with higher levels. Significant global associations were identified between vaccinia-specific interferon (IFN)-γ and DQA1 (P = .003), interleukin (IL)-1β and HLA-B (P = .004), tumor necrosis factor (TNF)-α and HLA-B (P = .006), and IL-6 and HLA-B locus (P = .016) for secreted cytokines, as well as between CD8α(+) IFN-γ Elispot responses and DQB1 (P = .027). Subjects carrying B3906 (P = .006) and B5701 (P < .001) secreted higher levels of IL-1β than did subjects who did not carry these alleles. Subjects carrying the B5301 (P = .047) and B5601 (P = .008) alleles secreted less IL-1β, compared with subjects who did not carry these alleles. The B3502 (P = .009), B5601 (P = .004), and B*5701 (P < .001) alleles were significantly associated with variations in TNF-α secretion.

CONCLUSIONS

These data suggest that variations in antibody and cellular IFN-γ, IL-1β, TNF-α, and IL-6 immune responses after receipt of smallpox vaccine are genetically controlled by HLA genes or genes in close linkage disequilibrium to these alleles.