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Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens

Nature Biotechnology volume 30, pages 883–888 (2012)Cite this article

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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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Figure 1: Mucosal adjuvant activity of PEI and protection from disease by mucosal pathogens.
Figure 2: Interactions between antigen and PEI, and between immune cells and PEI-antigen complexes.
Figure 3: PEI-induced host dsDNA release and cytoplasmic recognition by means of Irf3-dependent signaling.

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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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Author notes

  1. Neil C Sheppard

    Present address: Present address: Vaccine Research, Pfizer Inc., San Diego, California, USA.,

  2. Neil C Sheppard and Quentin J Sattentau: These authors contributed equally to this work.

Authors and Affiliations

  1. The Sir William Dunn School of Pathology, University of Oxford, Oxford, UK

    Frank Wegmann, Kate H Gartlan, Sarah A Brinckmann, Margherita Coccia, William R Hillson, George Krashias, Amin E Moghaddam, Neil C Sheppard & Quentin J Sattentau

  2. Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    Ali M Harandi

  3. The Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Oxford, UK

    Wai Ling Kok, Suzanne Cole & Ling-Pei Ho

  4. The Jenner Institute, The University of Oxford, Oxford, UK

    Teresa Lambe

  5. The Division of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden

    Manoj Puthia & Catharina Svanborg

  6. The Department of Immunology, University of Washington, Seattle, Washington, USA

    Erin M Scherer, Joseph N Blattman & Philip D Greenberg

  7. Yale School of Medicine, New Haven, Connecticut, USA

    Adam Williams & Richard A Flavell

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Contributions

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.

Corresponding author

Correspondence to Quentin J Sattentau.

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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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