Coatsome-replicon vehicles: Self-replicating RNA vaccines against infectious diseases.

Herein, we provide the first description of a synthetic delivery method for self-replicating replicon RNAs (RepRNA) derived from classical swine fever virus (CSFV) using a Coatsome-replicon vehicle based on Coatsome® SS technologies. This results in an unprecedented efficacy when compared to well-established polyplexes, with up to ∼65 fold-increase of the synthesis of RepRNA-encoded gene of interest (GOI). We demonstrated the efficacy of such Coatsome-replicon vehicles for RepRNA-mediated induction of CD8 T-cell responses in mice. Moreover, we provide new insights on physical properties of the RepRNA, showing that the removal of all CSFV structural protein genes has a positive effect on the translation of the GOI. Finally, we successfully engineered RepRNA constructs encoding a porcine reproductive and respiratory syndrome virus (PRRSV) antigen, providing an example of antigen expression with potential application to combat viral diseases. The versatility and simplicity of modifying and manufacturing these Coatsome-replicon vehicle formulations represents a major asset to tackle foreseeable emerging pandemics.
Competing Interests: Declaration of competing interest A patent for the application of delivery vehicles for the delivery of RepRNA vaccines to DCs using replicons derived from classical swine fever virus, as employed in this paper, has been filed in Europe and granted in USA, Canada, and India, with priority date of 4 June 2008. The filing was by Kenneth C. McCullough, Nicolas Ruggli and Jon Duri Tratschin (all three as inventors) (WO 2009146867), and assigned to their employer – the Institute of Virology and Immunology IVI. This does not alter the authors' adherence to the policies of sharing data and materials. Carlos A. Guzmán and Thomas Ebensen are named as inventors in a patent application covering the use of c-di-AMP as adjuvant (PCT/EP 2006010693).
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