Polyethylenimine-based polyplex delivery of self-replicating RNA vaccines

Demoulins, Thomas; Milona, Panagiota; Englezou, Pavlos; Ebensen, Thomas; Schulze, Kai; Suter, Rolf; Pichon, Chantal; Midoux, Patrick; Guzmán, Carlos A; Ruggli, Nicolas; McCullough, Kenneth (2015). Polyethylenimine-based polyplex delivery of self-replicating RNA vaccines. Nanomedicine : nanotechnology, biology, and medicine, 12(3), pp. 711-722. Elsevier 10.1016/j.nano.2015.11.001

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Self-amplifying replicon RNA (RepRNA) are large molecules (12-14kb); their self-replication amplifies mRNA template numbers, affording several rounds of antigen production, effectively increasing vaccine antigen payloads. Their sensitivity to RNase-sensitivity and inefficient uptake by dendritic cells (DCs) - absolute requirements for vaccine design - were tackled by condensing RepRNA into synthetic, nanoparticulate, polyethylenimine (PEI)-polyplex delivery vehicles. Polyplex-delivery formulations for small RNA molecules cannot be transferred to RepRNA due to its greater size and complexity; the N:P charge ratio and impact of RepRNA folding would influence polyplex condensation, post-delivery decompaction and the cytosolic release essential for RepRNA translation. Polyplex-formulations proved successful for delivery of RepRNA encoding influenza virus hemagglutinin and nucleocapsid to DCs. Cytosolic translocation was facilitated, leading to RepRNA translation. This efficacy was confirmed in vivo, inducing both humoral and cellular immune responses. Accordingly, this paper describes the first PEI-polyplexes providing efficient delivery of the complex and large, self-amplifying RepRNA vaccines.

Item Type:

Journal Article (Original Article)

Division/Institute:

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

UniBE Contributor:

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

Subjects:

600 Technology > 630 Agriculture

ISSN:

1549-9642

Publisher:

Elsevier

Language:

English

Submitter:

Barbara Gautschi-Steffen

Date Deposited:

29 Feb 2016 13:47

Last Modified:

26 Jun 2016 02:11

Publisher DOI:

10.1016/j.nano.2015.11.001

PubMed ID:

26592962

Uncontrolled Keywords:

Adjuvant; Blood dendritic cells; Humoral and cellular immunity; Influenza vaccines; Intracellular delivery; Polyplexes; Replicon-RNA; Self-replicating vaccine

BORIS DOI:

10.7892/boris.76054

URI:

https://boris.unibe.ch/id/eprint/76054

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