Polyethyleneimine is a potent systemic adjuvant for glycoprotein antigens

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 coformulated with CpG oligodeoxynucleotides, PEI adjuvant potency was synergistically increased and biased toward 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.

Exploring ‘new’ bioactivities of polymers at the nano–bio interface

“…The cationic polymer polyethyleneimine (PEI), long used as a carrier tool for gene transfection, was recently found to be a promising adjuvant [9,10] and was used as a direct therapeutic agent for immunotherapy [11][12][13]. As a potent mucosal adjuvant against viral subunit glycoprotein antigens [9,10], PEI co-administrated with viral vaccine antigen gp140 increased the production of antigen-specific IgG approximately 100 fold, compared to gp140 alone.…”

“…As a potent mucosal adjuvant against viral subunit glycoprotein antigens [9,10], PEI co-administrated with viral vaccine antigen gp140 increased the production of antigen-specific IgG approximately 100 fold, compared to gp140 alone. Size was crucial for the activity of PEI, because PEI of higher molecular weight (750 kDa) and in branched form acted more powerfully than lower molecular weight PEI and its linear form.…”

“…The complex was internalised by antigen-presenting cells (APCs) that subsequently induced non-proinflammatory cytokine release, which may be a major mechanism for the immune activity of PEI [10]. In addition to its adjuvant role, PEI was also able to induce cytokine expression that recruited APCs [9], inhibit the development of arthritis [12], as well as promote the response of type 1 T helper cells in vivo [11]. None of these diverse, immunemodulating activities of PEI has been found in its monomers.…”

H9N2 Influenza Whole Inactivated Virus Combined with Polyethyleneimine Strongly Enhances Mucosal and Systemic Immunity after Intranasal Immunization in Mice

“…Similarly, branched PEI is the best research form in terms of gene delivery (25). Recently, it was reported that branched PEI drove a mixed Th1/Th2-type adaptive immune response after systemic delivery (26).…”

APTES-modified nanosilica -- but neither APTES nor nanosilica -- inhibits endothelial cell growth via arrest of cell cycle at G1 phase

“…5 Reversely, the small monomers of ethylene glycol pose no effect on immune cells; but when they assemble into nano-to-micro-scale polymers, they further become complex with antigens and potently challenge the antigen-presenting cells. 6,7 As such, it is necessary to take a closer look at the toxicity of modifying agents in their relevant dimension, so as to provide more reliable information on the safer use of processed nanomaterials for biomedical purposes.…”