, Volume 67, Issue 10, pp 547–561 | Cite as

Single nucleotide polymorphisms/haplotypes associated with multiple rubella-specific immune response outcomes post-MMR immunization in healthy children

  • Inna G. Ovsyannikova
  • Hannah M. Salk
  • Beth R. Larrabee
  • V. Shane Pankratz
  • Gregory A. PolandEmail author
Original Paper


The observed heterogeneity in rubella-specific immune response phenotypes post-MMR vaccination is thought to be explained, in part, by inter-individual genetic variation. In this study, single nucleotide polymorphisms (SNPs) and multiple haplotypes in several candidate genes were analyzed for associations with more than one rubella-specific immune response outcome, including secreted IFN-γ, secreted IL-6, and neutralizing antibody titers. Overall, we identified 23 SNPs in 10 different genes that were significantly associated with at least two rubella-specific immune responses. Of these SNPs, we detected eight in the PVRL3 gene, five in the PVRL1 gene, one in the TRIM22 gene, two in the IL10RB gene, two in the TLR4 gene, and five in other genes (PVR, ADAR, ZFP57, MX1, and BTN2A1/BTN3A3). The PVRL3 gene haplotype GACGGGGGCAGCAAAAAGAAGAGGAAAGAACAA was significantly associated with both higher IFN-γ secretion (t-statistic 4.43, p < 0.0001) and higher neutralizing antibody titers (t-statistic 3.14, p = 0.002). Our results suggest that there is evidence of multigenic associations among identified gene SNPs and that polymorphisms in these candidate genes contribute to the overall observed differences between individuals in response to live rubella virus vaccine. These results will aid our understanding of mechanisms behind rubella-specific immune response to MMR vaccine and influence the development of vaccines in the future.


Rubella vaccine Single nucleotide polymorphisms (SNPs) Genetic association Neutralizing antibodies Cytokines 

MeSH Keywords

Rubella Rubella vaccine Rubella virus Measles-mumps-rubella vaccine Single nucleotide polymorphism Genetic association studies Antibodies Neutralizing Cytokines 



We thank the Mayo Clinic Vaccine Research Group staff and subjects who participated in our studies. We thank Caroline L. Vitse for her editorial assistance with this manuscript. We thank Nathaniel D. Warner for his assistance with this study. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers R37AI48793 (which recently received a MERIT Award) and R01AI33144. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health

Conflict of interest

Dr. Poland is the chair of a Safety Evaluation Committee for novel non-rubella investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland offers consultative advice on vaccine development to Merck & Co. Inc., CSL Biotherapies, Avianax, Sanofi Pasteur, Dynavax, Novartis Vaccines and Therapeutics, PAXVAX Inc., Emergent Biosolutions, Adjuvance, and Vaxess. Drs. Poland and Ovsyannikova hold two patents related to measles and vaccinia peptide research. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies.

Supplementary material

251_2015_864_MOESM1_ESM.docx (20 kb)
Table S1 (DOCX 19 kb)
251_2015_864_MOESM2_ESM.docx (16 kb)
Table S2 (DOCX 16 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Inna G. Ovsyannikova
    • 1
  • Hannah M. Salk
    • 1
  • Beth R. Larrabee
    • 2
  • V. Shane Pankratz
    • 2
  • Gregory A. Poland
    • 1
    Email author
  1. 1.Mayo Clinic Vaccine Research GroupMayo ClinicRochesterUSA
  2. 2.Department of Health Sciences ResearchMayo ClinicRochesterUSA

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