Systematic characterization of human response to H1N1 influenza vaccination through the construction and integration of personalized transcriptome response profiles

Abstract

Gene expression data is commonly used in vaccine studies to characterize differences between treatment groups or sampling time points. Group-wise comparisons of the transcriptional perturbations induced by vaccination have been applied extensively for investigating the mechanisms of action of vaccines. Such approaches, however, may not be sensitive enough for detecting changes occurring within a minority of the population under investigation or in single individuals. In this study, we developed a data analysis framework to characterize individual subject response profiles in the context of repeated measure experiments, which are typical of vaccine mode of action studies. Following the definition of the methodology, this was applied to the analysis of human transcriptome responses induced by vaccination with a subunit influenza vaccine. Results highlighted a substantial heterogeneity in how different subjects respond to vaccination. Moreover, the extent of transcriptional modulation experienced by each individual subject was found to be associated with the magnitude of vaccine-specific functional antibody response, pointing to a mechanistic link between genes involved in protein production and innate antiviral response. Overall, we propose that the improved characterization of the intersubject heterogeneity, enabled by our approach, can help driving the improvement and optimization of current and next-generation vaccines.