Dataset Information

Polymorphisms in the Wilms Tumor Gene Are Associated With Interindividual Variations in Rubella Virus-Specific Cellular Immunity After Measles-Mumps-Rubella II Vaccination.

ABSTRACT: Rubella vaccination induces widely variable immune responses in vaccine recipients. While rubella vaccination is effective at inducing immunity to rubella infection in most subjects, up to 5% of individuals do not achieve or maintain long-term protective immunity. To expand upon our previous work identifying genetic polymorphisms that are associated with these interindividual differences in humoral immunity to rubella virus, we performed a genome-wide association study in a large cohort of 1843 subjects to discover single-nucleotide polymorphisms (SNPs) associated with rubella virus-specific cellular immune responses. We identified SNPs in the Wilms tumor protein gene (WT1) that were significantly associated (P < 5 × 10-8) with interindividual variations in rubella-specific interleukin 6 secretion from subjects' peripheral blood mononuclear cells postvaccination. No SNPs were found to be significantly associated with variations in rubella-specific interferon-? secretion. Our findings demonstrate that genetic polymorphisms in the WT1 gene in subjects of European ancestry are associated with interindividual differences in rubella virus-specific cellular immunity after measles-mumps-rubella II vaccination.

SUBMITTER: Voigt EA

PROVIDER: S-EPMC5853945 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Polymorphisms in the Wilms Tumor Gene Are Associated With Interindividual Variations in Rubella Virus-Specific Cellular Immunity After Measles-Mumps-Rubella II Vaccination.

Voigt Emily A EA Haralambieva Iana H IH Larrabee Beth L BL Kennedy Richard B RB Ovsyannikova Inna G IG Schaid Daniel J DJ Poland Gregory A GA

The Journal of infectious diseases 20180101 4

Rubella vaccination induces widely variable immune responses in vaccine recipients. While rubella vaccination is effective at inducing immunity to rubella infection in most subjects, up to 5% of individuals do not achieve or maintain long-term protective immunity. To expand upon our previous work identifying genetic polymorphisms that are associated with these interindividual differences in humoral immunity to rubella virus, we performed a genome-wide association study in a large cohort of 1843 ...[more]

PMID: 29253144

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Project description:BackgroundThe reported coverage of the measles-rubella (MR) or measles-mumps-rubella (MMR) vaccine is greater than 99.0% in Zhejiang province. However, the incidence of measles, mumps, and rubella remains high. In this study, we assessed MMR seropositivity and disease distribution by age on the basis of the current vaccination program, wherein the first dose of MR is administered at 8 months and the second dose of MMR is administered at 18-24 months.MethodsCross-sectional serological surveys of MMR antibodies were conducted by collecting epidemiological data in Zhejiang province, China in 2011. In total, 1015 participants were randomly selected from two surveillance sites. Serum MMR-specific immunoglobulin G levels were tested by enzyme-linked immunosorbent assay. The geometric mean titers and seroprevalence with 95% confidence intervals (CIs) were calculated by age and gender. Proportions of different dose of vaccine by age by vaccine were also identified. Statistically significant differences between categories were assessed by the Chi-square test.ResultsOver 95% seroprevalence rates of measles were seen in all age groups except <7 months infants. Children aged 5-9 years were shown lower seropositivity rates of mumps while elder adolescences and young adults were presented lower rubella seroprevalence. Especially, rubella seropositivity was significantly lower in female adults than in male. Nine measles cases were unvaccinated or unknown vaccination history. Among them, 66.67% (6/9) patients were aged 20-29 years while 33.33% (3/9) were infants aged 8-12 months. In addition, 57.75% (648/1122) patients with mumps were children aged 5-9 years, and 50.54% (94/186) rubella cases were aged 15-39 years.ConclusionsA timely two-dose MMR vaccination schedule is recommended, with the first dose at 8 months and the second dose at 18-24 months. An MR vaccination speed-up campaign may be necessary for elder adolescents and young adults, particularly young females.

Project description:ImportanceThe US population is experiencing a resurgence of measles, with more than 1000 cases during the first 6 months of 2019. Imported measles cases among returning international travelers are the source of most US measles outbreaks, and these importations can be reduced with pretravel measles-mumps-rubella (MMR) vaccination of pediatric travelers. Although it is estimated that children account for less than 10% of US international travelers, pediatric travelers account for 47% of all known measles importations.ObjectiveTo examine clinical practice regarding MMR vaccination of pediatric international travelers and to identify reasons for nonvaccination of pediatric travelers identified as MMR eligible.Design, setting, and participantsThis cross-sectional study of pediatric travelers (ages ?6 months and <18 years) attending pretravel consultation at 29 sites associated with Global TravEpiNet (GTEN), a Centers for Disease Control and Prevention-supported consortium of clinical sites that provide pretravel consultations, was performed from January 1, 2009, through December 31, 2018.Main outcomes and measuresMeasles-mumps-rubella vaccination among MMR vaccination-eligible pediatric travelers.ResultsOf 14?602 pretravel consultations for pediatric international travelers, 2864 travelers (19.6%; 1475 [51.5%] males; 1389 [48.5%] females) were eligible to receive pretravel MMR vaccination at the time of the consultation: 365 of 398 infants aged 6 to 12 months (91.7%), 2161 of 3623 preschool-aged travelers aged 1 to 6 years (59.6%), and 338 of 10?581 school-aged travelers aged 6 to 18 years (3.2%). Of 2864 total MMR vaccination-eligible travelers, 1182 (41.3%) received the MMR vaccine and 1682 (58.7%) did not. The MMR vaccination-eligible travelers who did not receive vaccine included 161 of 365 infants (44.1%), 1222 of 2161 preschool-aged travelers (56.5%), and 299 of 338 school-aged travelers (88.5%). We observed a diversity of clinical practice at different GTEN sites. In multivariable analysis, MMR vaccination-eligible pediatric travelers were less likely to be vaccinated at the pretravel consultation if they were school-aged (model 1: odds ratio [OR], 0.32 [95% CI, 0.24-0.42; P?<?.001]; model 2: OR, 0.26 [95% CI, 0.14-0.47; P?<?.001]) or evaluated at specific GTEN sites (South: OR, 0.06 [95% CI, 0.01-0.52; P?<?.001]; West: OR, 0.10 [95% CI, 0.02-0.47; P?<?.001]). The most common reasons for nonvaccination were clinician decision not to administer MMR vaccine (621 of 1682 travelers [36.9%]) and guardian refusal (612 [36.4%]).Conclusions and relevanceAlthough most infant and preschool-aged travelers evaluated at GTEN sites were eligible for pretravel MMR vaccination, only 41.3% were vaccinated during pretravel consultation, mostly because of clinician decision or guardian refusal. Strategies may be needed to improve MMR vaccination among pediatric travelers and to reduce measles importations and outbreaks in the United States.

Project description:Measles outbreaks continue to occur in the United States and are mostly due to infections in returning travelers.To describe how providers assessed the measles immunity status of departing U.S. adult travelers seeking pretravel consultation and to assess reasons given for nonvaccination among those considered eligible to receive the measles, mumps, rubella (MMR) vaccine.Observational study in U.S. pretravel clinics.24 sites associated with Global TravEpiNet (GTEN), a Centers for Disease Control and Prevention-funded consortium.Adults (born in or after 1957) attending pretravel consultations at GTEN sites (2009 to 2014).Structured questionnaire completed by traveler and provider during pretravel consultation.40 810 adult travelers were included; providers considered 6612 (16%) to be eligible for MMR vaccine at the time of pretravel consultation. Of the MMR-eligible, 3477 (53%) were not vaccinated at the visit; of these, 1689 (48%) were not vaccinated because of traveler refusal, 966 (28%) because of provider decision, and 822 (24%) because of health systems barriers. Most MMR-eligible travelers who were not vaccinated were evaluated in the South (2262 travelers [65%]) or at nonacademic centers (1777 travelers [51%]). Nonvaccination due to traveler refusal was most frequent in the South (1432 travelers [63%]) and in nonacademic centers (1178 travelers [66%]).These estimates could underrepresent the opportunities for MMR vaccination because providers accepted verbal histories of disease and vaccination as evidence of immunity.Of U.S. adult travelers who presented for pretravel consultation at GTEN sites, 16% met criteria for MMR vaccination according to the provider's assessment, but fewer than half of these travelers were vaccinated. An increase in MMR vaccination of eligible U.S. adult travelers could reduce the likelihood of importation and transmission of measles virus.Centers for Disease Control and Prevention, National Institutes of Health, and the Steve and Deborah Gorlin MGH Research Scholars Award.

Dataset Information

Polymorphisms in the Wilms Tumor Gene Are Associated With Interindividual Variations in Rubella Virus-Specific Cellular Immunity After Measles-Mumps-Rubella II Vaccination.

Publications

Polymorphisms in the Wilms Tumor Gene Are Associated With Interindividual Variations in Rubella Virus-Specific Cellular Immunity After Measles-Mumps-Rubella II Vaccination.

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