Abstract
Protection against mucosally transmitted infections probably requires immunity at the site of pathogen entry1, yet there are no mucosal adjuvant formulations licensed for human use. Polyethyleneimine (PEI) represents a family of organic polycations used as nucleic acid transfection reagents in vitro and DNA vaccine delivery vehicles in vivo2,3. Here we show that diverse PEI forms have potent mucosal adjuvant activity for viral subunit glycoprotein antigens. A single intranasal administration of influenza hemagglutinin or herpes simplex virus type-2 (HSV-2) glycoprotein D with PEI elicited robust antibody-mediated protection from an otherwise lethal infection, and was superior to existing experimental mucosal adjuvants. PEI formed nanoscale complexes with antigen, which were taken up by antigen-presenting cells in vitro and in vivo, promoted dendritic cell trafficking to draining lymph nodes and induced non-proinflammatory cytokine responses. PEI adjuvanticity required release of host double-stranded DNA that triggered Irf3-dependent signaling. PEI therefore merits further investigation as a mucosal adjuvant for human use.
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Acknowledgements
This study was supported by grants from The MRC UK, The EU Network of Excellence 'Europrise', The International AIDS Vaccine Initiative Neutralizing Antibody Consortium (IAVI), The Bill and Melinda Gates Foundation Collaboration for Vaccine Design (CAVD), Dormeur Investment Service Ltd., the FP7-funded High Impact Project Advanced Immunization Technologies (ADITEC) and The EuroNanoMed-European Commission funded iNanoDCs. Q.J.S. is a Jenner Institute Investigator and a James Martin Senior Fellow.
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Q.J.S. conceived the study and N.C.S. provided initial proof of concept. F.W., K.H.G., S.A.B., N.C.S., A.M.H., M.C., W.R.H., W.L.K., S.C., T.L., M.P., E.M.S., G.K., A.W. and A.E.M. designed and performed experiments. Q.J.S., F.W. and K.H.G. wrote the paper. A.M.H., L.-P.H., C.S., J.N.B., P.D.G., R.A.F., A.E.M. and N.C.S. supplied reagents and made editorial suggestions.
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Wegmann, F., Gartlan, K., Harandi, A. et al. Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens. Nat Biotechnol 30, 883–888 (2012). https://doi.org/10.1038/nbt.2344
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DOI: https://doi.org/10.1038/nbt.2344
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