Vaccination is the most successful and cost-effective method to prevent infectious diseases. However, many vaccine antigens have poor in vivo immunogenic potential and need adjuvants to enhance immune response. The application of systems biology to immunity and vaccination has yield crucial insights about how vaccines and adjuvants work. We have previously characterized two safe and powerful delivery systems derived from non-pathogenic prokaryotic organisms: E2 and fd filamentous bacteriophage systems. They elicit immune response in vivo inducing CD8+ T-cell responses, even in the absence of adjuvants or stimuli for dendritic cells’ maturation. Nonetheless, a systematic and comparative analysis of the complex gene expression network underlying such activation is missing. Therefore, we compared the transcriptomes of ex vivo isolated bone marrow-derived dendritic cells exposed to these antigen delivery systems. Significant differences emerged, especially for genes involved in innate immunity, co-stimulation and cytokine production. Results indicate that E2 drives polarization toward Th2 phenotype, mainly mediated by Irf4, Ccl17 and Ccr4 over-expression. Conversely, fdscαDEC, triggers Th1 T cells' polarization through the induction of Il12b, Il12rb, Il6 and other molecules involved in its signal transduction. The data analysis was performed using RNASeqGUI, hence addressing the increasing need of transparency and reproducibility of computational analysis.