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Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens

Wegmann, Frank; Gartlan, Kate H.; Harandi, Ali M.; Brinckmann, Sarah A.; Coccia, Margherita; Hillson, William R.; Kok, Wai Ling; Cole, Suzanne; Ho, Ling-Pei and Lambe, Teresa, et al. (2012) In Nature Biotechnology 30(9). p.883-888
Abstract
Protection against mucosally transmitted infections probably requires immunity at the site of pathogen entry(1), 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(2,3). 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... (More)
Protection against mucosally transmitted infections probably requires immunity at the site of pathogen entry(1), 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(2,3). 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. (Less)
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Nature Biotechnology
volume
30
issue
9
pages
883 - 888
publisher
Nature Publishing Group
external identifiers
  • wos:000308705700023
  • scopus:84866103085
ISSN
1546-1696
DOI
10.1038/nbt.2344
language
English
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yes
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17cf6ca8-2899-4b7b-9c9d-c5b35669930d (old id 3283992)
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2013-01-07 09:42:41
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@article{17cf6ca8-2899-4b7b-9c9d-c5b35669930d,
  abstract     = {Protection against mucosally transmitted infections probably requires immunity at the site of pathogen entry(1), 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(2,3). 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.},
  author       = {Wegmann, Frank and Gartlan, Kate H. and Harandi, Ali M. and Brinckmann, Sarah A. and Coccia, Margherita and Hillson, William R. and Kok, Wai Ling and Cole, Suzanne and Ho, Ling-Pei and Lambe, Teresa and Puthia, Manoj and Svanborg, Catharina and Scherer, Erin M. and Krashias, George and Williams, Adam and Blattman, Joseph N. and Greenberg, Philip D. and Flavell, Richard A. and Moghaddam, Amin E. and Sheppard, Neil C. and Sattentau, Quentin J.},
  issn         = {1546-1696},
  language     = {eng},
  number       = {9},
  pages        = {883--888},
  publisher    = {Nature Publishing Group},
  series       = {Nature Biotechnology},
  title        = {Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens},
  url          = {http://dx.doi.org/10.1038/nbt.2344},
  volume       = {30},
  year         = {2012},
}