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Polyethyleneimine is a potent systemic adjuvant for glycoprotein antigens.

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Author

  • Neil C Sheppard
  • Sarah A Brinckmann
  • Kate H Gartlan
  • Manoj Puthia
  • Catharina Svanborg
  • George Krashias
  • Stephanie C Eisenbarth
  • Richard A Flavell
  • Quentin J Sattentau
  • Frank Wegmann

Summary, in English

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.

Publishing year

2014

Language

English

Pages

531-538

Publication/Series

International Immunology

Volume

26

Issue

10

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Immunology in the medical area

Status

Published

ISBN/ISSN/Other

  • ISSN: 1460-2377