Self-Replicating RNA Vaccine Delivery to Dendritic Cells.

Demoulins, Thomas; Englezou, Pavlos; Milona, Panagiota; Ruggli, Nicolas; Tirelli, Nicola; Pichon, Chantal; Sapet, Cédric; Ebensen, Thomas; Guzmán, Carlos A; McCullough, Kenneth (2017). Self-Replicating RNA Vaccine Delivery to Dendritic Cells. In: RNA Vaccines. Methods in molecular biology: Vol. 1499 (pp. 37-75). Springer 10.1007/978-1-4939-6481-9_3

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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.

Item Type:

Book Section (Book Chapter)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Demoulins, Thomas; Englezou, Pavlos; Milona, Panagiota; Ruggli, Nicolas and McCullough, Kenneth

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 630 Agriculture

ISSN:

1940-6029

ISBN:

978-1-4939-6479-6

Series:

Methods in molecular biology

Publisher:

Springer

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

06 Aug 2018 13:11

Last Modified:

20 Mar 2019 07:54

Publisher DOI:

10.1007/978-1-4939-6481-9_3

PubMed ID:

27987142

Uncontrolled Keywords:

Cationic lipids Chitosan nanoparticles Dendritic cell delivery Polyplexes Replicon-RNA Self-replicating vaccine Universal influenza vaccine

URI:

https://boris.unibe.ch/id/eprint/112047

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