title: Vesicular stomatitis virus replicon expressing the VP2 outer capsid protein of bluetongue virus serotype 8 induces complete protection of sheep against challenge infection.
abstract: Bluetongue virus (BTV) is an arthropod-borne pathogen that causes an often fatal, hemorrhagic disease in ruminants. Different BTV serotypes occur throughout many temperate and tropical regions of the world. In 2006, BTV serotype 8 (BTV-8) emerged in Central and Northern Europe for the first time. Although this outbreak was eventually controlled using inactivated virus vaccines, the epidemic caused significant economic losses not only from the disease in livestock but also from trade restrictions. To date, BTV vaccines that allow simple serological discrimination of infected and vaccinated animals (DIVA) have not been approved for use in livestock. In this study, we generated recombinant RNA replicon particles based on single-cycle vesicular stomatitis virus (VSV) vectors. Immunization of sheep with infectious VSV replicon particles expressing the outer capsid VP2 protein of BTV-8 resulted in induction of BTV-8 serotype-specific neutralizing antibodies. After challenge with a virulent BTV-8 strain, the vaccinated animals neither developed signs of disease nor showed viremia. In contrast, immunization of sheep with recombinant VP5 - the second outer capsid protein of BTV - did not confer protection. Discrimination of infected from vaccinated animals was readily achieved using an ELISA for detection of antibodies against the VP7 antigen. These data indicate that VSV replicon particles potentially represent a safe and efficacious vaccine platform with which to control future outbreaks by BTV-8 or other serotypes, especially in previously non-endemic regions where discrimination between vaccinated and infected animals is crucial.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kochinger
authors.forename: Nathalie
authors.initials: N
authors.lastname: Renevey
authors.forename: Martin A
authors.initials: MA
authors.lastname: Hofmann
authors.affiliation: Institute of Virology and Immunology (IVI), Sensemattstrasse 293, CH-3147 Mittelhäusern, Switzerland. gert.zimmer@ivi.admin.ch.
authors.forename: Gert
authors.initials: G
authors.lastname: Zimmer
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001819:Bluetongue / Q000517:prevention & control* / Q000821:virology; D001820:Bluetongue virus / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics* / Q000276:immunology; D005822:Genetic Vectors; D009500:Neutralization Tests / Q000662:veterinary; D012093:Replicon; D012756:Sheep; D012757:Sheep Diseases / Q000517:prevention & control* / Q000821:virology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D018116:Vesiculovirus / Q000235:genetics* / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; C442520:VP2 protein, Bluetongue virus; C488468:VP5 protein, Bluetongue virus; D014614:Vaccines, Synthetic; D014765:Viral Vaccines