title: Validation of a novel approach for the rapid production of immunogenic virus-like particles for bluetongue virus.
abstract: Bluetongue virus causes an emerging disease of ruminants, principally affecting sheep and cattle. Since 1998, there have been multiple separate outbreaks of bluetongue disease in Europe that have highlighted the need for a safe, efficacious, DIVA compliant vaccine. We report here a new baculovirus expression strategy which allowed pre-integration of the genes encoding the BTV inner capsid proteins at one baculovirus locus and those encoding the outer capsid proteins at a different locus. A modified baculovirus with two marker proteins to facilitate the phenotypic selection of recombinant viruses was developed. The utility of this approach is demonstrated by the production of BTV VLPs to a number of serotypes. For a proof of concept, VLPs of one serotype was then tested for protective immune response. VLPs were demonstrated to be safe, highly effective, immunogens in sheep, reducing post-challenge viraemia to levels below the threshold detection limit of quantitative RT-PCR when vaccinated animals were challenged with virulent virus.
authors.affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Stewart
authors.forename: Y
authors.initials: Y
authors.lastname: Bhatia
authors.forename: T N
authors.initials: TN
authors.lastname: Athmaran
authors.forename: R
authors.initials: R
authors.lastname: Noad
authors.forename: C
authors.initials: C
authors.lastname: Gastaldi
authors.forename: E
authors.initials: E
authors.lastname: Dubois
authors.forename: P
authors.initials: P
authors.lastname: Russo
authors.forename: R
authors.initials: R
authors.lastname: Thiéry
authors.forename: C
authors.initials: C
authors.lastname: Sailleau
authors.forename: E
authors.initials: E
authors.lastname: Bréard
authors.forename: S
authors.initials: S
authors.lastname: Zientara
authors.forename: P
authors.initials: P
authors.lastname: Roy
mesh_terms: D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001820:Bluetongue virus / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D008297:Male; D012756:Sheep; D022721:Vaccines, Virosome / Q000009:adverse effects / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology*; D014766:Viremia / Q000517:prevention & control; D022701:Virosomes / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*
chemical_list: D022721:Vaccines, Virosome; D014764:Viral Proteins; D014765:Viral Vaccines; D022701:Virosomes