Adenoviral Vector Vaccination Induces a Conserved Program of CD8+ T Cell Memory Differentiation in Mouse and Man

• Adenovector vaccination induces two transcriptionally distinct CD8 memory responses
• The sustained response induced by adenovectors and CMV is closely related
• The core molecular features are shared tightly in mouse and man
• Adenovaccines in humans induce a CD8 response that recapitulates these core features

SummaryFollowing exposure to vaccines, antigen-specific CD8+ T cell responses develop as long-term memory pools. 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 adenovector 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 upregulation of homing receptors and anti-apoptotic pathways, driven by conserved networks of transcription factors, including T-bet. In humans, an adenovirus vaccine induced similar CMV-like phenotypes and transcription factor regulation. These data clarify the core features of CD8+ T cell memory following vaccination with adenovectors and indicate a conserved pathway for memory development shared with persistent herpesviruses.

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