Type I IFN Counteracts the Induction of Antigen-specific Immune Responses by Lipid-based Delivery of MRNA Vaccines

Overview

Journal Mol Ther

Publisher Cell Press

Specialties Molecular Biology
Pharmacology

Date 2012 Sep 27

PMID 23011030

Citations 125

Authors

Charlotte Pollard

Joanna Rejman

Winni De Haes

Bernard Verrier

Ellen Van Gulck

Thomas Naessens

Stefaan De Smedt

Pieter Bogaert

Johan Grooten

Guido Vanham

Stefaan De Koker

Affiliations

Soon will be listed here.

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.

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References

Kariko K, Buckstein M, Ni H, Weissman D . Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity. 2005; 23(2):165-75. DOI: 10.1016/j.immuni.2005.06.008. View

Hoerr I, Obst R, Rammensee H, Jung G . In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies. Eur J Immunol. 1999; 30(1):1-7. DOI: 10.1002/1521-4141(200001)30:1<1::AID-IMMU1>3.0.CO;2-#. View

Kreiter S, Selmi A, Diken M, Koslowski M, Britten C, Huber C . Intranodal vaccination with naked antigen-encoding RNA elicits potent prophylactic and therapeutic antitumoral immunity. Cancer Res. 2010; 70(22):9031-40. DOI: 10.1158/0008-5472.CAN-10-0699. View

Brinkmann V, Geiger T, Alkan S, Heusser C . Interferon alpha increases the frequency of interferon gamma-producing human CD4+ T cells. J Exp Med. 1993; 178(5):1655-63. PMC: 2191249. DOI: 10.1084/jem.178.5.1655. View

Conry R, LoBuglio A, Wright M, Sumerel L, Pike M, Johanning F . Characterization of a messenger RNA polynucleotide vaccine vector. Cancer Res. 1995; 55(7):1397-400. View

Rajagopal D, Paturel C, Morel Y, Uematsu S, Akira S, Diebold S . Plasmacytoid dendritic cell-derived type I interferon is crucial for the adjuvant activity of Toll-like receptor 7 agonists. Blood. 2010; 115(10):1949-57. PMC: 2837337. DOI: 10.1182/blood-2009-08-238543. View

Kreiter S, Diken M, Selmi A, Tureci O, Sahin U . Tumor vaccination using messenger RNA: prospects of a future therapy. Curr Opin Immunol. 2011; 23(3):399-406. DOI: 10.1016/j.coi.2011.03.007. View

Klein U, Dalla-Favera R . Germinal centres: role in B-cell physiology and malignancy. Nat Rev Immunol. 2007; 8(1):22-33. DOI: 10.1038/nri2217. View

Jameson S, Masopust D . Diversity in T cell memory: an embarrassment of riches. Immunity. 2010; 31(6):859-71. PMC: 2957815. DOI: 10.1016/j.immuni.2009.11.007. View

10.

Van Gulck E, Van Tendeloo V, Berneman Z, Vanham G . Role of dendritic cells in HIV-immunotherapy. Curr HIV Res. 2010; 8(4):310-22. DOI: 10.2174/157016210791208631. View

11.

Bettinger T, Carlisle R, Read M, Ogris M, Seymour L . Peptide-mediated RNA delivery: a novel approach for enhanced transfection of primary and post-mitotic cells. Nucleic Acids Res. 2001; 29(18):3882-91. PMC: 55922. DOI: 10.1093/nar/29.18.3882. View

12.

Martinon F, Krishnan S, Lenzen G, Magne R, Gomard E, Guillet J . Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA. Eur J Immunol. 1993; 23(7):1719-22. DOI: 10.1002/eji.1830230749. View

13.

Scheel B, Aulwurm S, Probst J, Stitz L, Hoerr I, Rammensee H . Therapeutic anti-tumor immunity triggered by injections of immunostimulating single-stranded RNA. Eur J Immunol. 2006; 36(10):2807-16. DOI: 10.1002/eji.200635910. View

14.

Jafari M, Soltani M, Naahidi S, Karunaratne D, Chen P . Nonviral approach for targeted nucleic acid delivery. Curr Med Chem. 2012; 19(2):197-208. DOI: 10.2174/092986712803414141. View

15.

Havenar-Daughton C, Kolumam G, Murali-Krishna K . Cutting Edge: The direct action of type I IFN on CD4 T cells is critical for sustaining clonal expansion in response to a viral but not a bacterial infection. J Immunol. 2006; 176(6):3315-9. DOI: 10.4049/jimmunol.176.6.3315. View

16.

Van Gulck E, Ponsaerts P, Heyndrickx L, Vereecken K, Moerman F, De Roo A . Efficient stimulation of HIV-1-specific T cells using dendritic cells electroporated with mRNA encoding autologous HIV-1 Gag and Env proteins. Blood. 2005; 107(5):1818-27. DOI: 10.1182/blood-2005-01-0339. View

17.

Lu D, Benjamin R, Kim M, Conry R, Curiel D . Optimization of methods to achieve mRNA-mediated transfection of tumor cells in vitro and in vivo employing cationic liposome vectors. Cancer Gene Ther. 1994; 1(4):245-52. View

18.

Le Bon A, Durand V, Kamphuis E, Thompson C, Bulfone-Paus S, Rossmann C . Direct stimulation of T cells by type I IFN enhances the CD8+ T cell response during cross-priming. J Immunol. 2006; 176(8):4682-9. DOI: 10.4049/jimmunol.176.8.4682. View

19.

Kreiter S, Diken M, Selmi A, Diekmann J, Attig S, Husemann Y . FLT3 ligand enhances the cancer therapeutic potency of naked RNA vaccines. Cancer Res. 2011; 71(19):6132-42. DOI: 10.1158/0008-5472.CAN-11-0291. View

20.

Alexopoulou L, Holt A, Medzhitov R, Flavell R . Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature. 2001; 413(6857):732-8. DOI: 10.1038/35099560. View