Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens.
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...
Main Authors: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Journal article |
Language: | English |
Published: |
2012
|
_version_ | 1826289392801546240 |
---|---|
author | Wegmann, F Gartlan, K Harandi, A Brinckmann, SA Coccia, M Hillson, W Kok, W Cole, S Ho, L Lambe, T Puthia, M Svanborg, C Scherer, E Krashias, G Williams, A Blattman, J Greenberg, P Flavell, R Moghaddam, A Sheppard, N Sattentau, Q |
author_facet | Wegmann, F Gartlan, K Harandi, A Brinckmann, SA Coccia, M Hillson, W Kok, W Cole, S Ho, L Lambe, T Puthia, M Svanborg, C Scherer, E Krashias, G Williams, A Blattman, J Greenberg, P Flavell, R Moghaddam, A Sheppard, N Sattentau, Q |
author_sort | Wegmann, F |
collection | OXFORD |
description | 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. |
first_indexed | 2024-03-07T02:28:11Z |
format | Journal article |
id | oxford-uuid:a657a78c-b243-45ac-97d3-9106433d725d |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T02:28:11Z |
publishDate | 2012 |
record_format | dspace |
spelling | oxford-uuid:a657a78c-b243-45ac-97d3-9106433d725d2022-03-27T02:46:44ZPolyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a657a78c-b243-45ac-97d3-9106433d725dEnglishSymplectic Elements at Oxford2012Wegmann, FGartlan, KHarandi, ABrinckmann, SACoccia, MHillson, WKok, WCole, SHo, LLambe, TPuthia, MSvanborg, CScherer, EKrashias, GWilliams, ABlattman, JGreenberg, PFlavell, RMoghaddam, ASheppard, NSattentau, QProtection 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. |
spellingShingle | Wegmann, F Gartlan, K Harandi, A Brinckmann, SA Coccia, M Hillson, W Kok, W Cole, S Ho, L Lambe, T Puthia, M Svanborg, C Scherer, E Krashias, G Williams, A Blattman, J Greenberg, P Flavell, R Moghaddam, A Sheppard, N Sattentau, Q Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens. |
title | Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens. |
title_full | Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens. |
title_fullStr | Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens. |
title_full_unstemmed | Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens. |
title_short | Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens. |
title_sort | polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens |
work_keys_str_mv | AT wegmannf polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT gartlank polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT harandia polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT brinckmannsa polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT cocciam polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT hillsonw polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT kokw polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT coles polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT hol polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT lambet polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT puthiam polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT svanborgc polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT scherere polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT krashiasg polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT williamsa polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT blattmanj polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT greenbergp polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT flavellr polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT moghaddama polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT sheppardn polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens AT sattentauq polyethyleneimineisapotentmucosaladjuvantforviralglycoproteinantigens |