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)-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 = .047) and B*5601 (P = .008) alleles secreted less IL-1β, 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-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.

• Authors: Inna G Ovsyannikova, Robert A Vierkant, V Shane Pankratz, Robert M Jacobson, Gregory A Poland
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 203 Issue 11 Pg. 1546-55 (Jun 01 2011) ISSN: 1537-6613 [Electronic] United States
• PMID: 21592983 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Viral
• Cytokines
• DryVax vaccine
• HLA Antigens
• Smallpox Vaccine
• Tumor Necrosis Factor-alpha
• Interferon-gamma

Topics

• Adaptive Immunity (genetics, immunology)
• Adolescent
• Adult
• Antibodies, Viral (blood, immunology)
• Cytokines (blood, immunology, metabolism)
• Enzyme-Linked Immunospot Assay
• Female
• HLA Antigens (genetics, immunology)
• Humans
• Interferon-gamma (blood, immunology)
• Linear Models
• Male
• Multivariate Analysis
• Smallpox Vaccine (administration & dosage, immunology)
• Tumor Necrosis Factor-alpha (blood, immunology)