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Title: Type I IFN counteracts the induction of antigen-specific immune responses by lipid-based delivery of mRNA vaccines
Authors: Pollard, Charlotte ×
Rejman, Joanna
De Haes, Winni
Verrier, Bernard
Van Gulck, Ellen
Naessens, Thomas
De Smedt, Stefaan
Bogaert, Pieter
Grooten, Johan
Vanham, Guido
De Koker, Stefaan #
Issue Date: Jan-2013
Publisher: Academic Press
Series Title: Molecular Therapy vol:21 issue:1 pages:251-9
Article number: 10.1038/mt.2012.202
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-phosphoethanolamine (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.
ISSN: 1525-0016
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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