Polymorphisms in the Vitamin A Receptor and Innate Immunity Genes Influence the Antibody Response to Rubella Vaccination

Ovsyannikova, Inna G.; Haralambieva, Iana H.; Dhiman, Neelam; O’Byrne, Megan M.; Pankratz, V. Shane; Jacobson, Robert M.; Poland, Gregory A.

doi:10.1086/649588

Cited by 60 publications

(80 citation statements)

References 43 publications

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“…Our association study determined that the non-synonymous SNP rs3740996 in the TRIM5 gene was associated with rubella-specific antibody response (p=0.01). This specific SNP was found to have an important functional role (29)(30)(31). This same study also found 22 important associations (range of p values 0.002-0.05) between genetic variants in the vitamin A receptor family (RARA, RARB, and RARG), vitamin D receptor, RXRA genes, and rubella-specific (IFN-γ, IL-2, IL-10, TNF-α, and GM-CSF) cytokine responses (32).…”

Section: Innate Gene Polymorphisms and Vaccine Immunitymentioning

confidence: 54%

“…We studied the association of polymorphisms in these candidate innate IR genes to rubella vaccine-induced humoral and cellular immune responses. Overall, eight significant SNP associations (p<0.05) were found between the vitamin A (RARB), RIG-I, and TRIM (TRIM 5 and TRIM 22) genes and humoral immunity after rubella vaccine (29). Our association study determined that the non-synonymous SNP rs3740996 in the TRIM5 gene was associated with rubella-specific antibody response (p=0.01).…”

Section: Innate Gene Polymorphisms and Vaccine Immunitymentioning

confidence: 79%

“…Our recent study has shown that inter-individual variation in the HLA genes accounts for~20% of the overall genetic variation in rubella vaccine-induced antibodies (16). Guided by this understanding, we conducted a genotyping study in 738 children to determine associations between candidate SNPs and haplotypes and immune measures following two doses of rubella vaccine (25,29,32,36). Our data suggest that the variability of both rubella vaccineinduced humoral and cytokine responses is significantly modulated by cytokine and cytokine receptor genetic variants.…”

Section: Non-hla Genetic Polymorphisms and Vaccine Responsementioning

confidence: 91%

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Vaccinomics: Current Findings, Challenges and Novel Approaches for Vaccine Development

Ovsyannikova

2011

AAPS J

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Abstract. Recent years have witnessed a growing interest in a field of vaccinology that we have named vaccinomics. The overall idea behind vaccinomics is to identify genetic and other mechanisms and pathways that determine immune responses, and thereby provide new candidate vaccine approaches. Considerable data show that host genetic polymorphisms act as important determinants of innate and adaptive immunity to vaccines. This review highlights examples of the role of immunogenetics and immunogenomics in understanding immune responses to vaccination, which are highly variable across the population. The influence of HLA genes, non-HLA, and innate genes in inter-individual variations in immune responses to viral vaccines are examined using population-based gene/SNP association studies. The ability to understand relationships between immune response gene variants and vaccine-specific immunity may assist in designing new vaccines. At the same time, application of state-of-the-art nextgeneration sequencing technology (and bioinformatics) is desired to provide new genetic information and its relationship to the immune response.

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Section: Innate Gene Polymorphisms and Vaccine Immunitymentioning

confidence: 54%

Section: Innate Gene Polymorphisms and Vaccine Immunitymentioning

confidence: 79%

Section: Non-hla Genetic Polymorphisms and Vaccine Responsementioning

confidence: 91%

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Vaccinomics: Current Findings, Challenges and Novel Approaches for Vaccine Development

Ovsyannikova

2011

AAPS J

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“…Innate immunity also takes part in the response to viral pathogens, playing an important role in the initiation and modulation of adaptive immunity. For this reason, SNP associations were identified between the vitamin A (RARA, RARB, and RARG), RIG-I/DDX58, and TRIM genes and rubella vaccine-specific immunity (Ovsyannikova et al, 2010a(Ovsyannikova et al, , 2010b. Notably, the coding TRIM5 SNPs rs3740996 (previously found to affect TRIM5 antiviral activity) (Goldschmidt et al, 2006;Javanbakht et al, 2006;Sawyer et al, 2006;van Manen et al, 2008), rs3740996, and rs10838525 were associated with variations in rubella-specific humoral immunity, tumor necrosis factor (TNF)-a secretion, and IL-2/ GM-CSF production, respectively.…”

Section: The Case Of Immune Response Heterogeneity To Vaccinesmentioning

confidence: 99%

Vaccinomics and a New Paradigm for the Development of Preventive Vaccines Against Viral Infections

Poland

Ovsyannikova

Kennedy

et al. 2011

OMICS: A Journal of Integrative Biology

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“…Upon review of the data flagged by these thresholds, we are able to assess whether the interpolated value is likely to be an appropriate estimate of an individual's rubella virus-specific neutralizing antibody titers and therefore to decide whether or not it is appropriate to include the data in analyses. We have previously reported rubella virus-specific IgG levels using Beckman Coulter's Access Rubella IgG assay (12,(26)(27)(28)(29)(30). This assay calculates anti-rubella virus (strain HPV-77) titers based on a standard curve calibrated against the WHO 2nd International Standard Preparation for Anti-Rubella Serum.…”

Section: Fig 1 Distribution Of Initial Nt 50 Values Estimated As Thementioning

confidence: 99%

High-Throughput Assay Optimization and Statistical Interpolation of Rubella-Specific Neutralizing Antibody Titers

Lambert

Pankratz

Larrabee

et al. 2014

Clin. Vaccine Immunol.

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Rubella remains a social and economic burden due to the high incidence of congenital rubella syndrome (CRS) in some countries. For this reason, an accurate and efficient high-throughput measure of antibody response to vaccination is an important tool. In order to measure rubella-specific neutralizing antibodies in a large cohort of vaccinated individuals, a high-throughput immunocolorimetric system was developed. Statistical interpolation models were applied to the resulting titers to refine quantitative estimates of neutralizing antibody titers relative to the assayed neutralizing antibody dilutions. This assay, including the statistical methods developed, can be used to assess the neutralizing humoral immune response to rubella virus and may be adaptable for assessing the response to other viral vaccines and infectious agents.A cute infection with rubella virus usually results in a mild fever and rash. However, complications can arise when infection occurs during pregnancy. In this case, rubella virus is able to establish infection in the fetus, where there is up to a 90% risk of developing congenital rubella syndrome (CRS) if infection occurs during the first trimester (1, 2). Although vaccination programs have decreased the number of rubella cases and CRS in most countries, the burden of rubella and CRS is still high in many developing countries. Improved surveillance is needed to evaluate the progress of control programs (3).Traditional assays, like enzyme immunoassays (EIA), hemagglutination inhibition assays (HAI), and neutralization assays, have been successfully implemented for laboratory diagnostics and screening techniques. However, issues such as false positives, lack of sensitivity, standardization between platforms, and the time and resources needed to efficiently measure responses in a large number of samples still exist (4-10). Thus, a standard and efficient method that resolves some or all of these issues is needed. Our laboratories previously used a rubella virus-specific chemiluminescent immunoassay (Beckman Coulter Access, Brea, CA) and in-house colorimetry-and fluorescence-based immunoassays (Centers for Disease Control and Prevention [CDC]) to measure antibody titers to rubella virus. The chemiluminescent immunoassay produced highly sensitive and reproducible antibody titer data and revealed a large spectrum of antibody responses in individuals vaccinated against rubella virus (11,12). Although this quantifies rubella virus antibodies, the focus of our current study was to measure functional neutralizing antibodies against rubella virus.The first aim of this study was to adapt an immunocolorimetric system for the large-scale, high-throughput quantitation of rubella virus-neutralizing antibody in a cohort of 2,091 subjects and to test the level of precision between repeated results. Next, statistical approaches were used to interpolate these data into quantitative estimates of individual subject titer values that can be used as continuous measurements in subsequent analyses. Finally, correla...

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Polymorphisms in the Vitamin A Receptor and Innate Immunity Genes Influence the Antibody Response to Rubella Vaccination

Cited by 60 publications

References 43 publications

Vaccinomics: Current Findings, Challenges and Novel Approaches for Vaccine Development

Vaccinomics: Current Findings, Challenges and Novel Approaches for Vaccine Development

Vaccinomics and a New Paradigm for the Development of Preventive Vaccines Against Viral Infections

High-Throughput Assay Optimization and Statistical Interpolation of Rubella-Specific Neutralizing Antibody Titers

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