Title
Type I IFN counteracts the induction of antigen-specific immune responses by lipid-based delivery of mRNA vaccines Type I IFN counteracts the induction of antigen-specific immune responses by lipid-based delivery of mRNA vaccines
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
New York ,
Subject
Biology
Human medicine
Engineering sciences. Technology
Source (journal)
Molecular therapy. - New York
Volume/pages
21(2013) :1 , p. 251-259
ISSN
1525-0016
ISI
000313035000028
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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-3-trimethylammonium- 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. Received 3 April 2012; accepted 23 August 2012; advance online publication 25 September 2012. doi:10.1038/mt.2012.202
E-info
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