Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens

Frank Wegmann; Kate H. Gartlan; Ali M. Harandi; Sarah A. Brinckmann; Margherita Coccia; William R. Hillson; Wai Ling Kok; Suzanne Cole; Ling Pei Ho; Teresa Lambe; Manoj Puthia; Catharina Svanborg; Erin M. Scherer; George Krashias; Adam Williams; Joseph N. Blattman; Philip D. Greenberg; Richard A. Flavell; Amin E. Moghaddam; Neil C. Sheppard; Quentin J. Sattentau

doi:10.1038/nbt.2344

Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens

Frank Wegmann, Kate H. Gartlan, Ali M. Harandi, Sarah A. Brinckmann, Margherita Coccia, William R. Hillson, Wai Ling Kok, Suzanne Cole, Ling Pei Ho, Teresa Lambe, Manoj Puthia, Catharina Svanborg, Erin M. Scherer, George Krashias, Adam Williams, Joseph N. Blattman, Philip D. Greenberg, Richard A. Flavell, Amin E. Moghaddam, Neil C. SheppardQuentin J. Sattentau

Research output: Contribution to journal › Article › peer-review

181 Scopus citations

Abstract

Protection against mucosally transmitted infections probably requires immunity at the site of pathogen entry, 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 vivo. 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.

Original language	English (US)
Pages (from-to)	883-888
Number of pages	6
Journal	Nature biotechnology
Volume	30
Issue number	9
DOIs	https://doi.org/10.1038/nbt.2344
State	Published - Sep 2012
Externally published	Yes

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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Wegmann, F., Gartlan, K. H., Harandi, A. M., Brinckmann, S. A., Coccia, M., Hillson, W. R., Kok, W. L., Cole, S., Ho, L. P., Lambe, T., Puthia, M., Svanborg, C., Scherer, E. M., Krashias, G., Williams, A., Blattman, J. N., Greenberg, P. D., Flavell, R. A., Moghaddam, A. E., ... Sattentau, Q. J. (2012). Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens. Nature biotechnology, 30(9), 883-888. https://doi.org/10.1038/nbt.2344

Wegmann, F, Gartlan, KH, Harandi, AM, Brinckmann, SA, Coccia, M, Hillson, WR, Kok, WL, Cole, S, Ho, LP, Lambe, T, Puthia, M, Svanborg, C, Scherer, EM, Krashias, G, Williams, A, Blattman, JN, Greenberg, PD, Flavell, RA, Moghaddam, AE, Sheppard, NC & Sattentau, QJ 2012, 'Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens', Nature biotechnology, vol. 30, no. 9, pp. 883-888. https://doi.org/10.1038/nbt.2344

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title = "Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens",

abstract = "Protection against mucosally transmitted infections probably requires immunity at the site of pathogen entry, 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 vivo. 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.",

author = "Frank Wegmann and Gartlan, {Kate H.} and Harandi, {Ali M.} and Brinckmann, {Sarah A.} and Margherita Coccia and Hillson, {William R.} and Kok, {Wai Ling} and Suzanne Cole and Ho, {Ling Pei} and Teresa Lambe and Manoj Puthia and Catharina Svanborg and Scherer, {Erin M.} and George Krashias and Adam Williams and Blattman, {Joseph N.} and Greenberg, {Philip D.} and Flavell, {Richard A.} and Moghaddam, {Amin E.} and Sheppard, {Neil C.} and Sattentau, {Quentin J.}",

note = "Funding Information: This study was supported by grants from The MRC UK, The EU Network of Excellence {\textquoteleft}Europrise{\textquoteright}, 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.",

year = "2012",

month = sep,

doi = "10.1038/nbt.2344",

language = "English (US)",

volume = "30",

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AU - Wegmann, Frank

AU - Gartlan, Kate H.

AU - Harandi, Ali M.

AU - Brinckmann, Sarah A.

AU - Coccia, Margherita

AU - Hillson, William R.

AU - Kok, Wai Ling

AU - Cole, Suzanne

AU - Ho, Ling Pei

AU - Lambe, Teresa

AU - Puthia, Manoj

AU - Svanborg, Catharina

AU - Scherer, Erin M.

AU - Krashias, George

AU - Williams, Adam

AU - Blattman, Joseph N.

AU - Greenberg, Philip D.

AU - Flavell, Richard A.

AU - Moghaddam, Amin E.

AU - Sheppard, Neil C.

AU - Sattentau, Quentin J.

N1 - Funding Information: 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.

PY - 2012/9

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N2 - Protection against mucosally transmitted infections probably requires immunity at the site of pathogen entry, 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 vivo. 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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Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens

Abstract

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