Abstract
Background. Genetic association studies demonstrated a role for cytokine proteins and cytokine or cytokine receptor gene polymorphisms in smallpox vaccine-induced adaptive immunity.Methods. We examined the association of genetic polymorphisms with cellular (interferon [IFN] γ enzyme-linked immunospot assay [ELISPOT]) immune response to smallpox vaccine in 1076 immunized individuals.Results. The majority of significant associations were discovered between single-nucleotide polymorphisms/haplotypes in IL18R1 and IL18 genes, in which we previously reported an association with vaccinia virus-induced neutralizing antibody titers in this study cohort. A functional coding IL18R1 polymorphism (rs1035130/Phe251Phe; P =. 01) was significantly associated with an allele dose-related increase in IFN-γ production and was also associated with vaccinia-specific neutralizing antibody titers. Significant associations were also found between IL18R1 haplotypes and variations in IFN-γ ELISPOT responses (global P <. 0001).Conclusions. Our data suggest the importance of variants in the IL18R1 and IL18 genetic loci for broad-based smallpox vaccine-induced adaptive immunity.
Original language | English (US) |
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Pages (from-to) | 1422-1430 |
Number of pages | 9 |
Journal | Journal of Infectious Diseases |
Volume | 208 |
Issue number | 9 |
DOIs | |
State | Published - Nov 1 2013 |
Keywords
- African-Americans
- Polymorphism
- enzyme-linked immunospot assay
- european continental ancestry group
- genetic predisposition to disease
- genetic variation
- haplotypes
- interferon-gamma
- interleukin-18
- interleukin-18 receptor alpha subunit
- single nucleotide
- smallpox vaccine
- vaccinia virus
- viral vaccines
ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases