Adenoviral vector vaccination induces a conserved program of CD8+ T cell memory differentiation in mouse and man. Mus musculus

Following exposure to vaccines, antigen-specific CD8+ T-cell responses develop as long-term memory pools. Novel vaccine strategies based on adenoviral vectors, e.g. those developed for HCV, are able to induce and sustain substantial CD8+ T-cell populations. How such populations evolve following vaccination remains to be defined at a transcriptional level. We addressed the transcriptional regulation of divergent CD8+ T-cell memory pools induced by an adenoviral vector encoding a model antigen (beta-galactosidase). We observe transcriptional profiles that mimic those following infection with persistent pathogens, murine and human cytomegalovirus (CMV). Key transcriptional hallmarks include up-regulation of homing receptors, and anti-apoptotic pathways, driven by conserved networks of transcription factors, including T-bet (TBX21). In humans, a novel adenovirus vaccine induced similar CMV-like phenotypes and underlying transcription factor regulation. These data clarify the core features of CD8+ T-cell memory following vaccination with adenovirus vectors and indicate a conserved pathway for memory development shared with persistent herpesviruses. Overall design: Total RNA was extracted from sorted memory CD8 T cells induce by CMV and adenoviral vectors, and naïve CD8 cells