title: Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens.
abstract: 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.
authors.affiliation: The Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Wegmann
authors.forename: Kate H
authors.initials: KH
authors.lastname: Gartlan
authors.forename: Ali M
authors.initials: AM
authors.lastname: Harandi
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Brinckmann
authors.forename: Margherita
authors.initials: M
authors.lastname: Coccia
authors.forename: William R
authors.initials: WR
authors.lastname: Hillson
authors.forename: Wai Ling
authors.initials: WL
authors.lastname: Kok
authors.forename: Suzanne
authors.initials: S
authors.lastname: Cole
authors.forename: Ling-Pei
authors.initials: LP
authors.lastname: Ho
authors.forename: Teresa
authors.initials: T
authors.lastname: Lambe
authors.forename: Manoj
authors.initials: M
authors.lastname: Puthia
authors.forename: Catharina
authors.initials: C
authors.lastname: Svanborg
authors.forename: Erin M
authors.initials: EM
authors.lastname: Scherer
authors.forename: George
authors.initials: G
authors.lastname: Krashias
authors.forename: Adam
authors.initials: A
authors.lastname: Williams
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Blattman
authors.forename: Philip D
authors.initials: PD
authors.lastname: Greenberg
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Amin E
authors.initials: AE
authors.lastname: Moghaddam
authors.forename: Neil C
authors.initials: NC
authors.lastname: Sheppard
authors.forename: Quentin J
authors.initials: QJ
authors.lastname: Sattentau
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D001835:Body Weight; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D005260:Female; D006389:Hemagglutinins, Viral / Q000276:immunology; D018928:Immunity, Mucosal / Q000187:drug effects* / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology; D011094:Polyethyleneimine / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D014759:Viral Envelope Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000956:Antigens, Viral; D006389:Hemagglutinins, Viral; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C040570:glycoprotein D-herpes simplex virus type 2; C041524:aluminum sulfate; D011094:Polyethyleneimine; D004247:DNA