Introduction: The innate immunogenicity of lipid nanoparticle formulated self-amplifying RNA vaccines engenders protective immunity but also reactogenic side effects. By comparison, polymeric saRNA vaccine formulations achieve higher protein translation, lower inflammation, and weaker protective immunity.1,2 We hypothesized that adjuvanting polymeric saRNA with an antigen presenting cell (APC)-targeted STING agonizing polymeric prodrug (polySTING)3 would enable tailored augmentation of productive innate and adaptive immune responses with favorable tolerability compared to lipid nanoparticle saRNA.
Learning Objectives:
At the completion of this activity, participants will know
Understand how the biodistribution of polyplexes and lipid nanoparticles influence saRNA vaccination
Explain how innate responses contribute to vaccine efficacy and side effects
Compare strengths and weaknesses of polyplex and lipid nanoparticle RNA vaccines and therapies
