title: Application of bluetongue Disabled Infectious Single Animal (DISA) vaccine for different serotypes by VP2 exchange or incorporation of chimeric VP2.
abstract: Bluetongue is a disease of ruminants caused by the bluetongue virus (BTV). Bluetongue outbreaks can be controlled by vaccination, however, currently available vaccines have several drawbacks. Further, there are at least 26 BTV serotypes, with low cross protection. A next-generation vaccine based on live-attenuated BTV without expression of non-structural proteins NS3/NS3a, named Disabled Infectious Single Animal (DISA) vaccine, was recently developed for serotype 8 by exchange of the serotype determining outer capsid protein VP2. DISA vaccines are replicating vaccines but do not cause detectable viremia, and induce serotype specific protection. Here, we exchanged VP2 of laboratory strain BTV1 for VP2 of European serotypes 2, 4, 8 and 9 using reverse genetics, without observing large effects on virus growth. Exchange of VP2 from serotype 16 and 25 was however not possible. Therefore, chimeric VP2 proteins of BTV1 containing possible immunogenic regions of these serotypes were studied. BTV1, expressing 1/16 chimeric VP2 proteins was functional in virus replication in vitro and contained neutralizing epitopes of both serotype 1 and 16. For serotype 25 this approach failed. We combined VP2 exchange with the NS3/NS3a negative phenotype in BTV1 as previously described for serotype 8 DISA vaccine. DISA vaccine with 1/16 chimeric VP2 containing amino acid region 249-398 of serotype 16 raised antibodies in sheep neutralizing both BTV1 and BTV16. This suggests that DISA vaccine could be protective for both parental serotypes present in chimeric VP2. We here demonstrate the application of the BT DISA vaccine platform for several serotypes and further extend the application for serotypes that are unsuccessful in single VP2 exchange.
authors.affiliation: Department of Virology, Central Veterinary Institute of Wageningen UR (CVI), Lelystad, The Netherlands; Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. Electronic address: femke2.feenstra@wur.nl.
authors.forename: Femke
authors.initials: F
authors.lastname: Feenstra
authors.affiliation: Department of Virology, Central Veterinary Institute of Wageningen UR (CVI), Lelystad, The Netherlands.
authors.forename: Janny S
authors.initials: JS
authors.lastname: Pap
authors.affiliation: Department of Virology, Central Veterinary Institute of Wageningen UR (CVI), Lelystad, The Netherlands; Department of Biochemistry, Centre for Human Metabonomics, North-West University, South Africa.
authors.forename: Piet A
authors.initials: PA
authors.lastname: van Rijn
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000097:blood*; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D001819:Bluetongue / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D001820:Bluetongue virus / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D056738:Cross Protection; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D059386:Reverse Genetics; D065288:Serogroup; D012756:Sheep; D014611:Vaccination; D017361:Viral Nonstructural Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D000939:Epitopes; D011993:Recombinant Fusion Proteins; C075080:S10 protein, Bluetongue virus; C442520:VP2 protein, Bluetongue virus; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines
keywords: Bluetongue virus; Chimera; DISA vaccine; NS3/NS3a; Serotype; VP2