Bluetongue is a disease in ruminants caused by the bluetongue virus (BTV), and is spread by Culicoides biting midges.
Bluetongue outbreaks cause huge economic losses and death in sheep in several parts of the world. The most effective measure to control BTV is vaccination. However, both commercially available
vaccines and recently developed
vaccine candidates have several shortcomings. Therefore, we generated and tested next-generation
vaccines for
bluetongue based on the backbone of a laboratory-adapted strain of BTV-1, avirulent BTV-6 or virulent BTV-8. All
vaccine candidates were serotyped with VP2 of BTV-8 and did not express NS3/NS3a non-structural
proteins, due to induced deletions in the NS3/NS3a ORF. Sheep were vaccinated once with one of these
vaccine candidates and were challenged with virulent BTV-8 3 weeks after vaccination. The NS3/NS3a knockout mutation caused complete avirulence for all three BTV backbones, including for virulent BTV-8, indicating that safety is associated with the NS3/NS3a knockout phenotype. Viraemia of
vaccine virus was not detected using sensitive PCR diagnostics. Apparently, the
vaccine viruses replicated only locally, which will minimize spread by the insect vector. In particular, the
vaccine based on the BTV-6 backbone protected against disease and prevented viraemia of challenge virus, showing the efficacy of this
vaccine candidate. The lack of NS3/NS3a expression potentially enables the differentiation of infected from vaccinated animals, which is important for monitoring virus spread in vaccinated livestock. The disabled infectious single-animal
vaccine for
bluetongue presented here is very promising and will be the subject of future studies.