Harnessing ZBP1-driven cell death to improve influenza vaccine efficacy

Project Narrative Seasonal influenza A virus (IAV) infections account for up to 700,000 hospitalizations and 50,000 annual deaths in the US alone. Current vaccine strategies for seasonal IAV do not generate lasting immune responses, and vaccination approaches that provoke effective, long-lived cytotoxic T-cell-driven cellular immunity is still an unmet need. In this proposal, we outline a new approach to generating robust and lasting T-cell-mediated immunity to IAV that harnesses a recently-discovered immunogenic cell death modality activated by the sensor protein ZBP1.