Co-administration of GM-CSF expressing RNA is a powerful tool to enhance potency of SAM-based vaccines.

•SAM vaccines were engineered to express cytokine GM-CSF and influenza antigen NP.•Administration of GM-CSF increases recruitment of antigen presenting cells at site of injection.•Co-administration of SAM expressing cytokine increases antigen-specific CD8+ T-cell response.•Enhanced response translates in an increased protection in a mouse model of influenza infection.•Cytokines in SAM vaccine design may potentiate the effectiveness of RNA vaccination.