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Polyethyleneimine is a potent systemic adjuvant for glycoprotein antigens.

Sheppard, Neil C; Brinckmann, Sarah A; Gartlan, Kate H; Puthia, Manoj LU ; Svanborg, Catharina LU ; Krashias, George; Eisenbarth, Stephanie C; Flavell, Richard A; Sattentau, Quentin J and Wegmann, Frank (2014) In International Immunology 26(10). p.531-538
Abstract
Polyethyleneimine (PEI) is an organic polycation used extensively as a gene- and DNA vaccine delivery reagent. Although the DNA targeting activity of PEI is well documented, its immune activating activity is not. We recently reported that PEI has robust mucosal adjuvanticity when administered intranasally with glycoprotein antigens. Here we show that PEI has strong immune activating activity after systemic delivery. PEI administered subcutaneously with viral glycoprotein (HIV-1 gp140) enhanced antigen-specific serum IgG production in the context of mixed Th1/Th2-type immunity. PEI elicited higher titers of both antigen binding and neutralizing antibodies than alum in mice and rabbits, and induced an increased proportion of antibodies... (More)
Polyethyleneimine (PEI) is an organic polycation used extensively as a gene- and DNA vaccine delivery reagent. Although the DNA targeting activity of PEI is well documented, its immune activating activity is not. We recently reported that PEI has robust mucosal adjuvanticity when administered intranasally with glycoprotein antigens. Here we show that PEI has strong immune activating activity after systemic delivery. PEI administered subcutaneously with viral glycoprotein (HIV-1 gp140) enhanced antigen-specific serum IgG production in the context of mixed Th1/Th2-type immunity. PEI elicited higher titers of both antigen binding and neutralizing antibodies than alum in mice and rabbits, and induced an increased proportion of antibodies reactive with native antigen. In an intraperitoneal model, PEI recruited neutrophils followed by monocytes to the site of administration, and enhanced antigen uptake by antigen presenting cells. The Th bias was modulated by PEI activation of the Nlrp3 inflammasome, however its global adjuvanticity was unchanged in Nlrp3-deficient mice. When co-formulated with CpG oligodeoxynucleotides, PEI adjuvant potency was synergistically increased and biased towards a Th1-type immune profile. Taken together these data support the use of PEI as a versatile systemic adjuvant platform with particular utility for induction of secondary structure-reactive antibodies against glycoprotein antigens. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Immunology
volume
26
issue
10
pages
531 - 538
publisher
Oxford University Press
external identifiers
  • pmid:24844701
  • wos:000343321400001
  • scopus:84918835260
ISSN
1460-2377
DOI
10.1093/intimm/dxu055
language
English
LU publication?
yes
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baf7746d-01cb-4663-ac16-05a9df4d25f1 (old id 4454097)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24844701?dopt=Abstract
date added to LUP
2014-06-04 22:01:39
date last changed
2017-11-05 03:21:58
@article{baf7746d-01cb-4663-ac16-05a9df4d25f1,
  abstract     = {Polyethyleneimine (PEI) is an organic polycation used extensively as a gene- and DNA vaccine delivery reagent. Although the DNA targeting activity of PEI is well documented, its immune activating activity is not. We recently reported that PEI has robust mucosal adjuvanticity when administered intranasally with glycoprotein antigens. Here we show that PEI has strong immune activating activity after systemic delivery. PEI administered subcutaneously with viral glycoprotein (HIV-1 gp140) enhanced antigen-specific serum IgG production in the context of mixed Th1/Th2-type immunity. PEI elicited higher titers of both antigen binding and neutralizing antibodies than alum in mice and rabbits, and induced an increased proportion of antibodies reactive with native antigen. In an intraperitoneal model, PEI recruited neutrophils followed by monocytes to the site of administration, and enhanced antigen uptake by antigen presenting cells. The Th bias was modulated by PEI activation of the Nlrp3 inflammasome, however its global adjuvanticity was unchanged in Nlrp3-deficient mice. When co-formulated with CpG oligodeoxynucleotides, PEI adjuvant potency was synergistically increased and biased towards a Th1-type immune profile. Taken together these data support the use of PEI as a versatile systemic adjuvant platform with particular utility for induction of secondary structure-reactive antibodies against glycoprotein antigens.},
  author       = {Sheppard, Neil C and Brinckmann, Sarah A and Gartlan, Kate H and Puthia, Manoj and Svanborg, Catharina and Krashias, George and Eisenbarth, Stephanie C and Flavell, Richard A and Sattentau, Quentin J and Wegmann, Frank},
  issn         = {1460-2377},
  language     = {eng},
  number       = {10},
  pages        = {531--538},
  publisher    = {Oxford University Press},
  series       = {International Immunology},
  title        = {Polyethyleneimine is a potent systemic adjuvant for glycoprotein antigens.},
  url          = {http://dx.doi.org/10.1093/intimm/dxu055},
  volume       = {26},
  year         = {2014},
}