Lipoplexes carrying mRNA-encoding Gag protein modulate dendritic cells to stimulate HIV-specific immune responses

W. De Haes, J. Rejman, C. Pollard, C. Merlin, M. Vekemans, E. Florence, S.C. De Smedt, J. Grooten, G. Vanham, S. De Koker, E. Van Gulck

Research output: Contribution to journalA1: Web of Science-article

Abstract

Aim: Cationic lipids (Lipofectamine [Invitrogen, Merelbeke, Belgium] and 1,2-dioleoyl-3-trimethylammonium-propane/1,2-dioleoyl-sn-glycero-3-phosphoethanol amine) and polymers (jetPEI and in vivo-jetPEI [Polyplus-transfection, Illkirch, France]) were evaluated for their potential to deliver mRNA to monocyte-derived dendritic cells. Materials & methods: Lipoplexes and polyplexes, containing mRNA-encoding GFP or Gag protein, were incubated with human monocyte-derived dendritic cells and transfection efficiencies were assessed by flow cytometry. Results: Lipofectamine was by far the most efficient in mRNA delivery, therefore it was used in further experiments. Incubation of monocyte-derived dendritic cells isolated from HIV-1-positive donors with mRNA-encoding Gag protein complexed to Lipofectamine resulted in 50% transfection. Importantly, coculture of these Gag-transfected dendritic cells with autologous T cells induced an over tenfold expansion of IFN-gamma- and IL-2-secreting CD4(+) and CD8(+) T cells. Conclusion: Cationic lipid-mediated mRNA delivery may be a useful tool for therapeutic vaccination against HIV-1. This approach can be applied to develop vaccination strategies for other infectious diseases and cancer. Original submitted 26 January 2012; Revised submitted 17 April 2012.
Original languageEnglish
JournalNanomedicine
Volume8
Issue number1
Pages (from-to)77-87
Number of pages11
ISSN1743-5889
DOIs
Publication statusPublished - 2013

Keywords

  • Viral diseases
  • HIV
  • AIDS
  • Immune response
  • Dendritic cells
  • Lipids
  • Polymers
  • mRNA
  • Gag proteins
  • Lipofectamine
  • Drug development

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