BioProject

The effect of vaccination on the epigenome remains poorly characterized. In previous research, we identified an association between seroprotection against influenza and DNA methylation at sites associated with the RIG-1 signaling pathway, which recognizes viral double-stranded RNA and leads to a type I interferon response. More...

The effect of vaccination on the epigenome remains poorly characterized. In previous research, we identified an association between seroprotection against influenza and DNA methylation at sites associated with the RIG-1 signaling pathway, which recognizes viral double-stranded RNA and leads to a type I interferon response. However, these studies did not fully account for confounding factors including age, gender, and BMI, along with changes in cell type composition. Here, we studied the influenza vaccine response in a longitudinal cohort vaccinated over two consecutive years (2019–2020 and 2020–2021), using peripheral blood mononuclear cells and a targeted DNA methylation approach. To address the effects of multiple factors on the epigenome, we designed a multivariate multiple regression model that included seroprotection levels as quantified by the hemagglutination-inhibition (HAI) assay test. Our findings indicate that 179 methylation sites can be combined as potential signatures to predict seroprotection. These sites were not only enriched for genes involved in the regulation of the RIG-I signaling pathway, as found previously, but also enriched for other genes associated with innate immunity to viruses and the transcription factor binding sites of BRD4, which is known to impact T cell memory. We propose a model to suggest that the RIG-I pathway and BRD4 could potentially be modulated to improve immunization strategies. Overall design: As part of a longitudinal study led by the University of Georgia, Athens (UGA), a cohort of 690 individuals was recruited for five successive seasons from 2016 to 2020 (UGA 1-5) between the ages of 18 to 65 years old. Participants were administered the split-inactivated influenza vaccine, Fluzone, manufactured by Sanofi Pasteur. For this study, a subset comprising 42 participants, all of whom were enrolled in UGA 5 and had previously been part of the UGA4 season, were selected. DNA was isolated from each participant's blood samples using the standard phenol-chloroform extraction approach. Less...