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

(2013) MOLECULAR THERAPY. 21(1). p.251-259
Author
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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.
Keywords
CYTOTOXIC T-LYMPHOCYTES, DENDRITIC CELLS, RECOGNITION, VACCINATION, INTERFERON, ADJUVANT, VIVO, TRANSFECTION, STRANDED-RNA, CLONAL EXPANSION

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Citation

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MLA
Pollard, Charlotte, et al. “Type I IFN Counteracts the Induction of Antigen-Specific Immune Responses by Lipid-Based Delivery of MRNA Vaccines.” MOLECULAR THERAPY, vol. 21, no. 1, 2013, pp. 251–59, doi:10.1038/mt.2012.202.
APA
Pollard, C., Rejman, J., De Haes, W., Verrier, B., Van Gulck, E., Naessens, T., … De Koker, S. (2013). Type I IFN counteracts the induction of antigen-specific immune responses by lipid-based delivery of mRNA vaccines. MOLECULAR THERAPY, 21(1), 251–259. https://doi.org/10.1038/mt.2012.202
Chicago author-date
Pollard, Charlotte, Joanna Rejman, Winni De Haes, Bernard Verrier, Ellen Van Gulck, Thomas Naessens, Stefaan De Smedt, et al. 2013. “Type I IFN Counteracts the Induction of Antigen-Specific Immune Responses by Lipid-Based Delivery of MRNA Vaccines.” MOLECULAR THERAPY 21 (1): 251–59. https://doi.org/10.1038/mt.2012.202.
Chicago author-date (all authors)
Pollard, Charlotte, Joanna Rejman, Winni De Haes, Bernard Verrier, Ellen Van Gulck, Thomas Naessens, Stefaan De Smedt, Pieter Bogaert, Johan Grooten, Guido Vanham, and Stefaan De Koker. 2013. “Type I IFN Counteracts the Induction of Antigen-Specific Immune Responses by Lipid-Based Delivery of MRNA Vaccines.” MOLECULAR THERAPY 21 (1): 251–259. doi:10.1038/mt.2012.202.
Vancouver
1.
Pollard C, Rejman J, De Haes W, Verrier B, Van Gulck E, Naessens T, et al. Type I IFN counteracts the induction of antigen-specific immune responses by lipid-based delivery of mRNA vaccines. MOLECULAR THERAPY. 2013;21(1):251–9.
IEEE
[1]
C. Pollard et al., “Type I IFN counteracts the induction of antigen-specific immune responses by lipid-based delivery of mRNA vaccines,” MOLECULAR THERAPY, vol. 21, no. 1, pp. 251–259, 2013.
@article{3127240,
  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.}},
  author       = {{Pollard, Charlotte and Rejman, Joanna and De Haes, Winni and Verrier, Bernard and Van Gulck, Ellen and Naessens, Thomas and De Smedt, Stefaan and Bogaert, Pieter and Grooten, Johan and Vanham, Guido and De Koker, Stefaan}},
  issn         = {{1525-0016}},
  journal      = {{MOLECULAR THERAPY}},
  keywords     = {{CYTOTOXIC T-LYMPHOCYTES,DENDRITIC CELLS,RECOGNITION,VACCINATION,INTERFERON,ADJUVANT,VIVO,TRANSFECTION,STRANDED-RNA,CLONAL EXPANSION}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{251--259}},
  title        = {{Type I IFN counteracts the induction of antigen-specific immune responses by lipid-based delivery of mRNA vaccines}},
  url          = {{http://dx.doi.org/10.1038/mt.2012.202}},
  volume       = {{21}},
  year         = {{2013}},
}

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