TY - JOUR
T1 - Human leukocyte antigen genotypes in the genetic control of adaptive immune responses to smallpox vaccine
AU - Ovsyannikova, Inna G.
AU - Vierkant, Robert A.
AU - Pankratz, V. Shane
AU - Jacobson, Robert M.
AU - Poland, Gregory A.
N1 - Funding Information:
This project has been funded in whole or in part with Federal funds from the National Institute of Allergies and Infectious Diseases, National Institutes of Health, Department of Health and Human Services (HHSN266200400065C).
PY - 2011/6/1
Y1 - 2011/6/1
N2 - 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-B*1302 (P = .036), B*3802 (P = .011), DQB1*0302 (P = .015), and DQB1*0604 (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 B*3906 (P = .006) and B*5701 (P < .001) secreted higher levels of IL-1β than did subjects who did not carry these alleles. Subjects carrying the B*5301 (P 5 .047) and B*5601 (P = .008) alleles secreted less IL-1β, compared with subjects who did not carry these alleles. The B*3502 (P 5 .009), B*5601 (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.
AB - 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-B*1302 (P = .036), B*3802 (P = .011), DQB1*0302 (P = .015), and DQB1*0604 (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 B*3906 (P = .006) and B*5701 (P < .001) secreted higher levels of IL-1β than did subjects who did not carry these alleles. Subjects carrying the B*5301 (P 5 .047) and B*5601 (P = .008) alleles secreted less IL-1β, compared with subjects who did not carry these alleles. The B*3502 (P 5 .009), B*5601 (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.
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U2 - 10.1093/infdis/jir167
DO - 10.1093/infdis/jir167
M3 - Article
C2 - 21592983
AN - SCOPUS:79956226254
SN - 0022-1899
VL - 203
SP - 1546
EP - 1555
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 11
ER -