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

Inna G. Ovsyannikova, Robert A. Vierkant, V. Shane Pankratz, Robert M. Jacobson, Gregory A. Poland

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1546-1555
Number of pages10
JournalJournal of Infectious Diseases
Volume203
Issue number11
DOIs
StatePublished - Jun 1 2011

Fingerprint

Smallpox Vaccine
Adaptive Immunity
HLA Antigens
Genotype
Alleles
Interleukin-1
Interferons
Vaccinia
Tumor Necrosis Factor-alpha
Interleukin-6
Genes
Antibodies
Linkage Disequilibrium
Cytokines

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Ovsyannikova, I. G., Vierkant, R. A., Pankratz, V. S., Jacobson, R. M., & Poland, G. A. (2011). Human leukocyte antigen genotypes in the genetic control of adaptive immune responses to smallpox vaccine. Journal of Infectious Diseases, 203(11), 1546-1555. https://doi.org/10.1093/infdis/jir167

Human leukocyte antigen genotypes in the genetic control of adaptive immune responses to smallpox vaccine. / Ovsyannikova, Inna G.; Vierkant, Robert A.; Pankratz, V. Shane; Jacobson, Robert M.; Poland, Gregory A.

In: Journal of Infectious Diseases, Vol. 203, No. 11, 01.06.2011, p. 1546-1555.

Research output: Contribution to journalArticle

Ovsyannikova, IG, Vierkant, RA, Pankratz, VS, Jacobson, RM & Poland, GA 2011, 'Human leukocyte antigen genotypes in the genetic control of adaptive immune responses to smallpox vaccine', Journal of Infectious Diseases, vol. 203, no. 11, pp. 1546-1555. https://doi.org/10.1093/infdis/jir167
Ovsyannikova, Inna G. ; Vierkant, Robert A. ; Pankratz, V. Shane ; Jacobson, Robert M. ; Poland, Gregory A. / Human leukocyte antigen genotypes in the genetic control of adaptive immune responses to smallpox vaccine. In: Journal of Infectious Diseases. 2011 ; Vol. 203, No. 11. pp. 1546-1555.
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abstract = "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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AU - Jacobson, Robert M.

AU - Poland, Gregory A.

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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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