Polyethyleneimine is a potent mucosal adjuvant for glycoproteins with innate and adaptive immune activating properties

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 entry(1). Polyethyleneimines (PEI) are organic polycations used as nucleic acid transfection reagents in vitro, and gene and DNA vaccine delivery vehicles in vivo(2, 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.