Type I IFN counteracts the induction of antigen-specific immune responses by lipid-based delivery of mRNA vaccines

C. Pollard, J. Rejman, W. De Haes, B. Verrier, E. Van Gulck, T. Naessens, S. De Smedt, P. Bogaert, J. Grooten, G. Vanham, S. De Koker

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

Abstract

The use of DNA and viral vector-based vaccines for the induction of cellular immune responses is increasingly gaining interest. However, concerns have been raised regarding the safety of these immunization strategies. Due to the lack of their genome integration, mRNA-based vaccines have emerged as a promising alternative. In this study, we evaluated the potency of antigen-encoding mRNA complexed with the cationic lipid 1,2-dioleoyl-3trimethylammonium-propane/1,2-dioleoyl-sn-glycero-3-phosphoethanola mine (DOTAP/DOPE ) as a novel vaccination approach. We demonstrate that subcutaneous immunization of mice with mRNA encoding the HIV-1 antigen Gag complexed with DOTAP/DOPE elicits antigen-specific, functional T cell responses resulting in specific killing of Gag peptide-pulsed cells and the induction of humoral responses. In addition, we show that DOTAP/DOPE complexed antigen-encoding mRNA displays immune-activating properties characterized by secretion of type I interferon (IFN) and the recruitment of proinflammatory monocytes to the draining lymph nodes. Finally, we demonstrate that type I IFN inhibit the expression of DOTAP/DOPE complexed antigen-encoding mRNA and the subsequent induction of antigen-specific immune responses. These results are of high relevance as they will stimulate the design and development of improved mRNA-based vaccination approaches.Molecular Therapy (2012); doi:10.1038/mt.2012.202.
Original languageEnglish
JournalMolecular Therapy
Volume21
Issue number1
Pages (from-to)251-259
Number of pages9
ISSN1525-0016
DOIs
Publication statusPublished - 2013

Keywords

  • Viral diseases
  • HIV-1
  • Vaccine development
  • Gag
  • mRNA
  • Antigens
  • T cells
  • Immune activation
  • Feasibility
  • Laboratory animals
  • Mice
  • In vivo
  • Inhibition

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