Genome-wide genetic associations with IFNγ response to smallpox vaccine

Richard B. Kennedy, Inna G. Ovsyannikova, V. Shane Pankratz, Iana H. Haralambieva, Robert A. Vierkant, Robert M. Jacobson, Gregory A. Poland

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32 Scopus citations

Abstract

Smallpox is a deadly and debilitating disease that killed hundreds of millions of people in the past century alone. The use of Vaccinia virus-based smallpox vaccines led to the eradication of smallpox. These vaccines are remarkably effective, inducing the characteristic pustule or "take" at the vaccine site in >97 % of recipients, and inducing a wide spectrum of long-lasting humoral and cellular immune responses. The mechanisms behind interindividual vaccine-response variability are likely to involve host genetic variation, but have not been fully characterized. We report here the first smallpox vaccine response genome-wide association study of over 1,000 recent recipients of Dryvax ®. The data presented here focus on cellular immune responses as measured by both production of secreted IFNy and quantitation of IFNy secreting cells by ELISPOT assay. We identified multiple significant SNP associations in genes (RASA1, ADRA1D, TCF7L1, FAS) that are critical components of signaling pathways that directly control lymphocyte IFNγ production or cytotoxic T cell function. Similarly, we found many associations with SNPs located in genes integral to nerve cell function; findings that, given the complex interplay between the nervous and immune systems, deserve closer examination in follow-up studies.

Original languageEnglish (US)
Pages (from-to)1433-1451
Number of pages19
JournalHuman genetics
Volume131
Issue number9
DOIs
StatePublished - Sep 1 2012

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Kennedy, R. B., Ovsyannikova, I. G., Shane Pankratz, V., Haralambieva, I. H., Vierkant, R. A., Jacobson, R. M., & Poland, G. A. (2012). Genome-wide genetic associations with IFNγ response to smallpox vaccine. Human genetics, 131(9), 1433-1451. https://doi.org/10.1007/s00439-012-1179-x