Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Frank Wegmann
  • Kate H. Gartlan
  • Ali M. Harandi
  • Sarah A. Brinckmann
  • Margherita Coccia
  • William R. Hillson
  • Wai Ling Kok
  • Suzanne Cole
  • Ling-Pei Ho
  • Teresa Lambe
  • Erin M. Scherer
  • George Krashias
  • Adam Williams
  • Joseph N. Blattman
  • Philip D. Greenberg
  • Richard A. Flavell
  • Amin E. Moghaddam
  • Neil C. Sheppard
  • Quentin J. Sattentau
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Mikrobiologi inom det medicinska området
  • Immunologi inom det medicinska området
Originalspråkengelska
Sidor (från-till)883-888
TidskriftNature Biotechnology
Volym30
Utgåva nummer9
StatusPublished - 2012
PublikationskategoriForskning
Peer review utfördJa