Project description:Whole blood transcriptomics analysis of healthy individuals, immunized with the MVA-B vaccine via transcutaneous or intramuscular route. We define an early gene expression profile, detected at day 1 and day 7 after immunization, that is associated with the development of either MVA specific humoral or CD8 T cell responses. We used System Biology approach to analyse vaccine efficacy in order to find innate predictive biomarkers of the quality of adaptive responses for potential clinical use in the future. Moreover, from a methodological point of view this study increases knowledges on how vaccine route(s) can affect resulting immune responses and into mechanisms involved in the induction of humoral and cellular immunity to vaccine.
Project description:The biological underpinnings of post-traumatic stress disorder (PTSD) have not been fully elucidated. Previous work suggests that alterations in the immune system are characteristic of the disorder. Identifying the biological mechanisms by which such alterations occur could provide fundamental insights into the etiology and treatment of PTSD. Here we identify specific epigenetic profiles underlying immune system changes associated with PTSD. Using blood samples (n=100) obtained from an ongoing, prospective epidemiologic study in Detroit, the Detroit Neighborhood Health Study (DNHS), we applied methylation microarrays to assay CpG sites from over 14,000 genes among 23 PTSD-affected and 77 PTSD-unaffected individuals. We show that immune system functions are significantly overrepresented among the annotations associated with genes uniquely unmethylated among those with PTSD. We further demonstrate that genes whose methylation levels are significantly and negatively correlated with traumatic burden show a similar strong signal of immune function among the PTSD-affected. The observed epigenetic variability in immune function by PTSD is corroborated using an independent biological marker of immune response to infection, cytomegalovirus—a typically latent herpesvirus whose activity was significantly higher among those with PTSD. These results provide the first report of peripheral epigenomic and CMV profiles associated with mental illness and suggest a new biological model of PTSD etiology in which an externally experienced traumatic event induces downstream alterations in immune function by reducing methylation levels of immune-related genes. Bisulfite conversion of whole blood-derived DNA samples was performed using the EZ-96 DNA methylation kit from Zymo Research. One microgram (μg) of each sample (including controls) was subjected to bisulfite conversion following manufacturer’s recommended protocol. 100 samples were analyzed of which 23 are PTSD affected and 77 are PTSD-unaffected. There were four technical replicates comprised of duplicate samples of two randomly selected individuals from the n=100 and duplicate samples of the control human methylated and unmethylated DNA.
