title: Genetic polymorphisms associated with rubella virus-specific cellular immunity following MMR vaccination.
abstract: 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.
authors.affiliation: Mayo Vaccine Research Group, Mayo Clinic, Guggenheim 611C, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Kennedy
authors.forename: Inna G
authors.initials: IG
authors.lastname: Ovsyannikova
authors.forename: Iana H
authors.initials: IH
authors.lastname: Haralambieva
authors.forename: Nathaniel D
authors.initials: ND
authors.lastname: Lambert
authors.forename: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Poland
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D016207:Cytokines / Q000276:immunology; D005260:Female; D005838:Genotype; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics*; D008297:Male; D022542:Measles-Mumps-Rubella Vaccine / Q000276:immunology*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018121:Receptors, Cytokine / Q000276:immunology; D012409:Rubella / Q000517:prevention & control*; D012412:Rubella virus / Q000276:immunology*; D013045:Species Specificity; D014611:Vaccination; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D016207:Cytokines; D022542:Measles-Mumps-Rubella Vaccine; D018121:Receptors, Cytokine
references.citation: Genes Immun. 2007 Oct;8(7):570-6
references.pmid: 17703179
references.citation: Hepatology. 2009 Jun;49(6):1847-58
references.pmid: 19434718
references.citation: Vaccine. 2009 Nov 16;27(49):6926-31
references.pmid: 19761839
references.citation: PLoS One. 2010 Jul 27;5(7):e11806
references.pmid: 20668555
references.citation: Nature. 2011 Aug 10;476(7359):214-9
references.pmid: 21833088
references.citation: J Infect Dis. 2011 Jun 1;203(11):1546-55
references.pmid: 21592983
references.citation: MMWR Recomm Rep. 2010 May 7;59(RR-3):1-12
references.pmid: 20448530
references.citation: J Infect Dis. 2007 Jan 1;195(1):21-9
references.pmid: 17152005
references.citation: Cytokine. 2010 Apr;50(1):24-9
references.pmid: 20117947
references.citation: Curr Opin Cell Biol. 2004 Oct;16(5):513-21
references.pmid: 15363801
references.citation: Tissue Antigens. 2008 Sep;72(3):211-20
references.pmid: 18715339
references.citation: J Biol Chem. 2005 Feb 18;280(7):5994-6004
references.pmid: 15572357
references.citation: Vaccine. 2009 May 26;27(25-26):3359-66
references.pmid: 19200845
references.citation: Hum Immunol. 2004 Dec;65(12):1506-15
references.pmid: 15603879
references.citation: BMC Immunol. 2010 Oct 05;11:48
references.pmid: 20923569
references.citation: PLoS One. 2010 Oct 14;5(10):e13384
references.pmid: 20976276
references.citation: J Exp Med. 2003 Aug 18;198(4):557-67
references.pmid: 12913096
references.citation: Vaccine. 1999 May 14;17(19):2356-65
references.pmid: 10392617
references.citation: J Immunol. 2004 Apr 1;172(7):3994-8
references.pmid: 15034010
references.citation: Vaccine. 2012 Apr 26;30(20):3082-9
references.pmid: 22406278
references.citation: Hum Genet. 2010 Feb;127(2):207-21
references.pmid: 19902255
references.citation: Pharmacogenomics. 2006 Jul;7(5):697-709
references.pmid: 16886895
references.citation: Vaccine. 2009 Jul 23;27(34):4656-61
references.pmid: 19520201
references.citation: MMWR Morb Mortal Wkly Rep. 2013 Jun 14;62(23):457-62
references.pmid: 23760185
references.citation: Vaccine. 2012 Mar 9;30(12):2146-52
references.pmid: 22285888
references.citation: Tissue Antigens. 2013 Jul;82(1):21-5
references.pmid: 23745570
references.citation: Paediatr Child Health. 2009 Dec;19(Suppl 2):S156-S159
references.pmid: 20976024
references.citation: Gene. 2012 Nov 15;510(1):59-65
references.pmid: 23009887
references.citation: Am J Hum Genet. 2004 Jan;74(1):106-20
references.pmid: 14681826
references.citation: Nat Immunol. 2009 Jan;10(1):48-57
references.pmid: 19011627
references.citation: Hum Hered. 2011;72(3):206-23
references.pmid: 22086389
references.citation: Pediatrics. 2010 Jul;126(1):e1-8
references.pmid: 20587679
references.citation: Hum Immunol. 2010 Apr;71(4):383-91
references.pmid: 20079393
references.citation: J Infect Dis. 2010 Jan 15;201(2):207-13
references.pmid: 20001730
references.citation: BMC Bioinformatics. 2011 May 02;12:129
references.pmid: 21535878
references.citation: Infect Immun. 1975 Apr;11(4):748-53
references.pmid: 1120613
references.citation: J Infect Dis. 2005 Feb 15;191(4):515-9
references.pmid: 15655774
references.citation: Hum Immunol. 2010 Feb;71(2):128-35
references.pmid: 19896518
references.citation: Vaccine. 2011 Nov 8;29(48):8988-97
references.pmid: 21939710
references.citation: Immunogenetics. 2010 Apr;62(4):197-210
references.pmid: 20217072
references.citation: Clin Exp Immunol. 1974 Aug;17(4):665-71
references.pmid: 4619795
references.citation: Vaccine. 2009 May 26;27(25-26):3319-23
references.pmid: 19200827
references.citation: Cell Mol Immunol. 2010 Jan;7(1):11-9
references.pmid: 20081873
references.citation: J Infect Dis. 2006 Mar 1;193(5):655-63
references.pmid: 16453260
references.citation: Epidemiol Infect. 2012 Dec;140(12):2290-301
references.pmid: 22335852