TY - JOUR
T1 - Genetic polymorphisms associated with rubella virus-specific cellular immunity following MMR vaccination
AU - Kennedy, Richard B.
AU - Ovsyannikova, Inna G.
AU - Haralambieva, Iana H.
AU - Lambert, Nathaniel D.
AU - Pankratz, V. Shane
AU - Poland, Gregory A.
N1 - Funding Information:
Acknowledgments We appreciate the study subjects and their families’ willingness to participate in our study. We thank the Mayo Clinic nurses and study coordinators for their efforts in subject recruitment, Dr. Julie M. Cunningham and the Mayo Medical Genome Facility Genotyping Core for their assistance with genotyp-ing efforts. We also thank Megan M. O’Byrne, Nathaniel D. Warner for their contributions to the statistical analyses. Research reported in this publication was supported by the National Institutes of Health, under award number AI033144, and the National Institute of Allergy And Infectious Diseases of the National Institutes of Health under award number R37 AI048793, which recently received a MERIT award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2014, Springer-Verlag Berlin Heidelberg.
PY - 2014/10/4
Y1 - 2014/10/4
N2 - Rubella virus causes a relatively benign disease in most cases, although infection during pregnancy can result in serious birth defects. An effective vaccine has been available since the early 1970s and outbreaks typically do not occur among highly vaccinated (≥2 doses) populations. Nevertheless, considerable inter-individual variation in immune response to rubella immunization does exist, with single-dose seroconversion rates ~95 %. Understanding the mechanisms behind this variability may provide important insights into rubella immunity. In the current study, we examined associations between single nucleotide polymorphisms (SNPs) in selected cytokine, cytokine receptor, and innate/antiviral genes and immune responses following rubella vaccination in order to understand genetic influences on vaccine response. Our approach consisted of a discovery cohort of 887 subjects aged 11–22 at the time of enrollment and a replication cohort of 542 older adolescents and young adults (age 18–40). Our data indicate that SNPs near the butyrophilin genes (BTN3A3/BTN2A1) and cytokine receptors (IL10RB/IFNAR1) are associated with variations in IFNγ secretion and that multiple SNPs in the PVR gene, as well as SNPs located in the ADAR gene, exhibit significant associations with rubella virus-specific IL-6 secretion. This information may be useful, not only in furthering our understanding immune responses to rubella vaccine, but also in identifying key pathways for targeted adjuvant use to boost immunity in those with weak or absent immunity following vaccination.
AB - Rubella virus causes a relatively benign disease in most cases, although infection during pregnancy can result in serious birth defects. An effective vaccine has been available since the early 1970s and outbreaks typically do not occur among highly vaccinated (≥2 doses) populations. Nevertheless, considerable inter-individual variation in immune response to rubella immunization does exist, with single-dose seroconversion rates ~95 %. Understanding the mechanisms behind this variability may provide important insights into rubella immunity. In the current study, we examined associations between single nucleotide polymorphisms (SNPs) in selected cytokine, cytokine receptor, and innate/antiviral genes and immune responses following rubella vaccination in order to understand genetic influences on vaccine response. Our approach consisted of a discovery cohort of 887 subjects aged 11–22 at the time of enrollment and a replication cohort of 542 older adolescents and young adults (age 18–40). Our data indicate that SNPs near the butyrophilin genes (BTN3A3/BTN2A1) and cytokine receptors (IL10RB/IFNAR1) are associated with variations in IFNγ secretion and that multiple SNPs in the PVR gene, as well as SNPs located in the ADAR gene, exhibit significant associations with rubella virus-specific IL-6 secretion. This information may be useful, not only in furthering our understanding immune responses to rubella vaccine, but also in identifying key pathways for targeted adjuvant use to boost immunity in those with weak or absent immunity following vaccination.
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U2 - 10.1007/s00439-014-1471-z
DO - 10.1007/s00439-014-1471-z
M3 - Article
C2 - 25098560
AN - SCOPUS:84919462097
VL - 133
SP - 1407
EP - 1417
JO - Human Genetics
JF - Human Genetics
SN - 0340-6717
IS - 11
ER -