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Self-Replicating RNA Vaccine Delivery to Dendritic Cells

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RNA Vaccines

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1499))

Abstract

Most current vaccines are either inactivated pathogen-derived or protein/peptide-based, although attenuated and vector vaccines have also been developed. The former induce at best moderate protection, even as multimeric antigen, due to limitations in antigen loads and therefore capacity for inducing robust immune defense. While attenuated and vector vaccines offer advantages through their replicative nature, drawbacks and risks remain with potential reversion to virulence and interference from preexisting immunity. New advances averting these problems are combining self-amplifying replicon RNA (RepRNA) technology with nanotechnology. RepRNA are large self-replicating RNA molecules (12–15 kb) derived from viral genomes defective in at least one structural protein gene. They provide sustained antigen production, effectively increasing vaccine antigen payloads over time, without the risk of producing infectious progeny. The major limitation with RepRNA is RNase-sensitivity and inefficient uptake by dendritic cells (DCs)—absolute requirements for efficacious vaccine design. We employed biodegradable delivery vehicles to protect the RepRNA and promote DC delivery. Encapsulating RepRNA into chitosan nanoparticles, as well as condensing RepRNA with polyethylenimine (PEI), cationic lipids, or chitosans, has proven effective for delivery to DCs and induction of immune responses in vivo.

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Acknowledgement

We thank Markus Gerber and Samira Locher for their help and input with the RepRNA technology, and Brigitte Herrmann for helping with the DC studies. We are also grateful to Patrick Midoux and Laure Magrangeas-Janot for help with the polyplex technology, Olivier Zelphati and Florent Poulhes for help with the lipoplex technology, and Kai Schulze for the adaptive immune response profiling. The work was funded by the Marie Curie IAPP Project Replixcel (251420) and the EU FP7 Project UniVax (HEALTH-F3-2013-60173).

Author information

Authors and Affiliations

  1. Institute of Virology and Immunology (IVI), Sensemattstrasse 293, CH-3147, Mittelhäusern, Switzerland

    Thomas Démoulins, Pavlos C. Englezou, Panagiota Milona, Nicolas Ruggli & Kenneth C. McCullough

  2. Centre of Regenerative Medicine, University of Manchester, Manchester, M13 9PT, UK

    Nicola Tirelli

  3. Centre de Biophysique Moléculaire, CNRS UPR4301, 45071, Orléans cedex 2, France

    Chantal Pichon

  4. OzBiosciences, Parc scientifique de Luminy, Marseille, France

    Cédric Sapet

  5. Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany

    Thomas Ebensen & Carlos A. Guzmán

Authors
  1. Thomas Démoulins
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  2. Pavlos C. Englezou
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  3. Panagiota Milona
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  4. Nicolas Ruggli
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  5. Nicola Tirelli
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  6. Chantal Pichon
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  7. Cédric Sapet
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  8. Thomas Ebensen
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  9. Carlos A. Guzmán
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  10. Kenneth C. McCullough
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Corresponding author

Correspondence to Thomas Démoulins .

Editor information

Editors and Affiliations

  1. Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany

    Thomas Kramps

  2. Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany

    Knut Elbers

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Démoulins, T. et al. (2017). Self-Replicating RNA Vaccine Delivery to Dendritic Cells. In: Kramps, T., Elbers, K. (eds) RNA Vaccines. Methods in Molecular Biology, vol 1499. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6481-9_3

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  • DOI: https://doi.org/10.1007/978-1-4939-6481-9_3

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6479-6

  • Online ISBN: 978-1-4939-6481-9

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