Bluetongue virus serotype 8 virus-like particles protect sheep against virulent virus infection as a single or multi-serotype cocktail immunogen

Since 1998, there have been multiple separate outbreaks of Bluetongue disease (BT) in Europe with the largest outbreak ever recorded in Northern Europe caused by Bluetongue virus serotype 8 (BTV-8). Coinciding with the BTV-8 outbreak, a virulent strain of BTV-1 emerged and co-infections of these two serotypes were reported. In response, we generated VLPs for BTV-8 and tested the efficacy of BTV-8 VLPs as a single immunogen and as a component of a multivalent vaccine, with VLPs of BTV-1 and BTV-2, in order to test if there was any interference between serotypes. All pre-Alps sheep vaccinated with BTV-8 VLPs developed a strong neutralising antibody response to BTV-8 and multivalent VLP vaccinated animals also developed neutralising antibodies to BTV-1 and BTV-2. There were no side effects observed due to the vaccination with either the single- or multivalent VLP cocktail. All VLP-vaccinated animals had no clinical manifestation of BT or viraemia after challenge with a virulent BTV-8 isolate. This data indicates that BTV-8 VLPs delivered as a single immunogen or as a component of a multivalent vaccine are highly efficacious. Moreover, there was no interference on the development of a strong protective immune response due to the combination of different phylogenetically unrelated BTV serotypes in the vaccinated animals. This report further highlights that BTV VLPs are safe and efficacious immunogens that are able to afford complete protection against a virulent virus challenge