Genetic variation in IL18R1 and IL18 genes and inteferon γ ELISPOT response to smallpox vaccination: An unexpected relationship

Inna G. Ovsyannikova, Iana H. Haralambieva, Richard B. Kennedy, Megan M. O'byrne, V. Shane Pankratz, Gregory A. Poland

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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 languageEnglish (US)
Pages (from-to)1422-1430
Number of pages9
JournalJournal of Infectious Diseases
Issue number9
StatePublished - Nov 1 2013


  • 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


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