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Polymorphisms in HLA-DPB1 are associated with differences in rubella virus-specific humoral immunity after vaccination.

ABSTRACT: Vaccination with live attenuated rubella virus induces a strong immune response in most individuals. However, small numbers of subjects never reach or maintain protective antibody levels, and there is a high degree of variability in immune response. We have previously described genetic polymorphisms in HLA and other candidate genes that are associated with interindividual differences in humoral immunity to rubella virus. To expand our previous work, we performed a genome-wide association study (GWAS) to discover single-nucleotide polymorphisms (SNPs) associated with rubella virus-specific neutralizing antibodies. We identified rs2064479 in the HLA-DPB1 genetic region as being significantly associated with humoral immune response variations after rubella vaccination (P = 8.62 × 10(-8)). All other significant SNPs in this GWAS were located near the HLA-DPB1 gene (P ? 1 × 10(-7)). These findings demonstrate that polymorphisms in HLA-DPB1 are strongly associated with interindividual differences in neutralizing antibody levels to rubella vaccination and represent a validation of our previous HLA work.

SUBMITTER: Lambert ND

PROVIDER: S-EPMC4351364 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Polymorphisms in HLA-DPB1 are associated with differences in rubella virus-specific humoral immunity after vaccination.

Lambert Nathaniel D ND Haralambieva Iana H IH Kennedy Richard B RB Ovsyannikova Inna G IG Pankratz Vernon Shane VS Poland Gregory A GA

The Journal of infectious diseases 20141006 6

Vaccination with live attenuated rubella virus induces a strong immune response in most individuals. However, small numbers of subjects never reach or maintain protective antibody levels, and there is a high degree of variability in immune response. We have previously described genetic polymorphisms in HLA and other candidate genes that are associated with interindividual differences in humoral immunity to rubella virus. To expand our previous work, we performed a genome-wide association study ( ...[more]

PMID: 25293367

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Project description:In the U.S., measles, mumps, and rubella vaccination is recommended as two vaccine doses. A third dose of measles-mumps-rubella (MMR) vaccine is being administered in certain situations (e.g., identified seronegativity and during outbreaks). We studied rubella-specific humoral immunity (neutralizing antibody, enzyme-linked immunosorbent assay/ELISA IgG titer and antibody avidity) and the frequencies of antigen-specific memory B cells before and after a third dose of MMR-II in 109 female participants of childbearing age (median age, 34.5 years old) from Olmsted County, MN, with two documented prior MMR vaccine doses. The participants were selected from a cohort of 1117 individuals if they represented the high and the low ends of the rubella-specific antibody response spectrum. Of the 109 participants, we identified four individuals (3.67% of all study participants; 7.14% of the low-responder group) that were seronegative at Baseline (rubella-specific ELISA IgG titers <10 IU/mL), suggesting a lack of protection against rubella before receipt of a third MMR vaccine dose. The peak geometric mean neutralizing antibody titer one month following the third dose of MMR vaccine for the cohort was 243 NT50 (CI; 241, 245), which is expected for a cohort with two doses of MMR, and the peak geometric mean IgG titer was 150 IU/mL (CI; 148, 152) with no seronegative individuals at Day 28. One-third of all subjects (31.8% for the neutralizing antibody; 30.8% for the IgG titer) experienced a significant boost (≥4-fold) of antibody titers one month following vaccination. Antibody titers and other tested immune-response variables were significantly higher in the high-responder group compared to the low-responder group. The frequencies of rubella-specific memory B cells were modestly associated with the antibody titers. Our study suggests the importance of yet unknown inherent biologic and immune factors for the generation and maintenance of rubella-vaccine-induced humoral immune responses.

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Polymorphisms in HLA-DPB1 are associated with differences in rubella virus-specific humoral immunity after vaccination.

Publications

Polymorphisms in HLA-DPB1 are associated with differences in rubella virus-specific humoral immunity after vaccination.

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