 there are no mucosal adjuvant formulations licensed for human use , despite protection against many mucosally - transmitted infections probably requiring immunity at the site of pathogen entry1 . polyethyleneimines ( pei ) 
 are organic polycations used as nucleic acid transfection reagents in vitro , and gene and dna vaccine delivery vehicles in vivo2 , 3 . here 
 we show that pei has unexpected and unusually potent mucosal adjuvant activity in conjunction with viral subunit glycoprotein antigens . 
 single intranasal administration of influenza ha or hsv-2 gd with pei elicited robust protection from otherwise lethal infection , and was superior to existing experimental mucosal adjuvants . 
 pei formed nanoscale complexes with antigen that were taken up by antigen presenting cells in vitro and in vivo , promoted dc trafficking to draining lymph nodes and induced non - proinflammatory cytokine responses . 
 pei adjuvanticity required release of host dsdna that triggered irf-3-dependent signaling . 
 pei therefore merits further investigation as a mucosal adjuvant for human use . 
Supplementary Material