Neuartige rekombinante Impfstoffe gegen die klassische Schweinepest auf der Basis der Replikon- Technologie

• Forschungsstelle: BLV
• Projektnummer: 1.07.07
• Projekttitel Englisch: Novel recombinant classical swine fever vaccines based on replicon-technology and vaccine delivery

Schlüsselwörter (Englisch)

Pestivirus, CSF, CSFV, virus replicon vaccines, vaccine delivery

Kurzbeschreibung (Englisch)

The aim of this project is to extend current developments on particulate classical swine fever virus vaccines based on replicon RNA. Replicons represent defective genomes that are able to replicate in host cells and express their encoded proteins. At the same time, replicons are incapable of forming replication-competent virus due to the lack of one or more genes encoding viral structural proteins. Accordingly, replicon vaccines are attenuated and non-transmissible, thereby fulfilling the requirements for a modern and safe vaccine. In the present project, replicon vaccine technology will be extended to generate replicons lacking the viral N^pro gene, an inhibitor of the primary immune response. These DN^pro replicons will be investigated in terms of the immune response they can induce, compared with replicons carrying the N^pro gene. For delivery of the material the replicon RNA will be packaged into virus particles using cells complementing for the respective missing structural protein of the virus as well as a novel proprietary delivery system. All experimental vaccines will be tested for their immunogenicity using established in vitro systems before vaccination trials in pigs. The vaccine will be designed for transdermal application using a gene gun devise appropriate for mass immunization of pigs.

Projektziele (Englisch)

The project includes two major goals:
(1). Improved efficacy of the replicon vaccine. This will investigate the value of deleting the N^pro gene from the replicon, the applicability of co-expressing immunological adjuvants, and the immunological advantage of employing cytopathogenic replicons.
(2). Delivery of the replicon RNA vaccine, precluding the need for packaging into virus particles. This approach will apply biodegradable nanoparticles as carrier material for the replicon RNA.

For both formulations of the replicon vaccine, either based on viral particles or on nanoparticles, the vaccine will be developed for transdermal application using the VetJet™ (Merial Ltd.), suitable for mass immunization.

Umsetzung und Anwendungen (Englisch)

Due to the epidemiological situation of CSF in Europe and the high economical impact of the disease the development of efficacious and safe vaccines that could be used for instance for emergency vaccination are justified. The development of nanoparticle-based RNA vaccines is novel. If it turns out to be usefull and efficacious, it is expected to be of interest beyond the field of CSFV and veterinary vaccinology.

Publikationen / Ergebnisse (Englisch)

Suter, R.; Summerfield, A.; Harwood, L.J.; McCullough, K.C.; Tratschin, J.-D.; Ruggli, N. (2010) Immunogenic and replicative properties of classical swine fever virus replicon particles modified to induce IFN-α/β and carry foreign genes. Submitted.

Suter, R. (2010) Classical swine fever virus replicon particles: a versatile and robust system for vaccine and gene expression applications. PhD thesis, GCB of the University of Berne, in preparation.

Suter, R.; Summerfield, A.; Harwood, L.J.; McCullough, K.; Tratschin, J.-D.; Ruggli, N. (2011) Immunogenic and replicative properties of classical swine fever virus replicon particles modified to induce IFN-/ and carry foreign genes. Vaccine 29, 1491–1503.

Zugehörige Dokumente

• 1.07.07 Datenblatt MJB2011, Tratschin [PDF] 85 kB