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

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)-? and DQA1 (P = .003), interleukin (IL)-1? and HLA-B (P = .004), tumor necrosis factor (TNF)-? and HLA-B (P = .006), and IL-6 and HLA-B locus (P = .016) for secreted cytokines, as well as between CD8?(+) IFN-? Elispot responses and DQB1 (P = .027). Subjects carrying B*3906 (P = .006) and B*5701 (P < .001) secreted higher levels of IL-1? than did subjects who did not carry these alleles. Subjects carrying the B*5301 (P = .047) and B*5601 (P = .008) alleles secreted less IL-1?, compared with subjects who did not carry these alleles. The B*3502 (P = .009), B*5601 (P = .004), and B*5701 (P < .001) alleles were significantly associated with variations in TNF-? secretion. CONCLUSIONS: These data suggest that variations in antibody and cellular IFN-?, IL-1?, TNF-?, 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.

SUBMITTER: Ovsyannikova IG

PROVIDER: S-EPMC3096794 | biostudies-other | 2011 Jun

REPOSITORIES: biostudies-other

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

Ovsyannikova Inna G IG Vierkant Robert A RA Pankratz V Shane VS Jacobson Robert M RM Poland Gregory A GA

The Journal of infectious diseases 20110601 11

<h4>Background</h4>The role of human leukocyte antigen (HLA) genes in mediating adaptive immune responses to smallpox vaccine remains unknown.<h4>Methods</h4>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.<h4>Results</h4>We found significant associations between the HLA-B and HLA - ...[more]

PMID: 21592983

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Project description:Mumps outbreaks continue to occur throughout the world, including in highly vaccinated populations. Vaccination against mumps has been successful; however, humoral and cellular immune responses to mumps vaccines vary significantly from person to person. We set out to assess whether HLA and cytokine gene polymorphisms are associated with variations in the immune response to mumps viral vaccine.To identify genetic factors that might contribute to variations in mumps vaccine-induced immune responses, we performed HLA genotyping in a group of 346 healthy schoolchildren (12-18 years of age) who previously received 2 doses of live mumps vaccine. Single-nucleotide polymorphisms (minor allele frequency of >5%) in cytokine and cytokine receptor genes were genotyped for a subset of 118 children.Median values for mumps-specific antibody titers and lymphoproliferative stimulation indices were 729 IU/mL and 4.8, respectively. Girls demonstrated significantly higher mumps antibody titers than boys, indicating gender-linked genetic differences in humoral immune response. Significant associations were found between the HLA-DQB1*0303 alleles and lower mumps-specific antibody titers. An interesting finding was the association of several HLA class II alleles with mumps-specific lymphoproliferation. Alleles of the DRB1 (*0101, *0301, *0801, *1001, *1201, and *1302), DQA1 (*0101, *0105, *0401, and *0501), and DQB1 (*0201, *0402, and *0501) loci were associated with significant variations in lymphoproliferative immune responses to mumps vaccine. Additional associations were observed with single-nucleotide polymorphisms in the interleukin-10RA, interleukin-12RB1, and interleukin-12RB2 cytokine receptor genes. Minor alleles for 4 single-nucleotide polymorphisms within interleukin-10RA and interleukin-12RB genes were associated with variations in humoral and cellular immune responses to mumps vaccination.These data suggest the important role of HLA and immunoregulatory cytokine receptor gene polymorphisms in explaining variations in mumps vaccine-induced immune responses.

Dataset Information

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

Publications

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

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