title: Strong protection induced by an experimental DIVA subunit vaccine against bluetongue virus serotype 8 in cattle.
abstract: Bluetongue virus (BTV) infections in ruminants pose a permanent agricultural threat since new serotypes are constantly emerging in new locations. Clinical disease is mainly observed in sheep, but cattle were unusually affected during an outbreak of BTV seroype 8 (BTV-8) in Europe. We previously developed an experimental vaccine based on recombinant viral protein 2 (VP2) of BTV-8 and non-structural proteins 1 (NS1) and NS2 of BTV-2, mixed with an immunostimulating complex (ISCOM)-matrix adjuvant. We demonstrated that bovine immune responses induced by this vaccine were as good or superior to those induced by a classic commercial inactivated vaccine. In this study, we evaluated the protective efficacy of the experimental vaccine in cattle and, based on the detection of VP7 antibodies, assessed its DIVA compliancy following virus challenge. Two groups of BTV-seronegative calves were subcutaneously immunized twice at a 3-week interval with the subunit vaccine (n=6) or with adjuvant alone (n=6). Following BTV-8 challenge 3 weeks after second immunization, controls developed viremia and fever associated with other mild clinical signs of bluetongue disease, whereas vaccinated animals were clinically and virologically protected. The vaccine-induced protection was likely mediated by high virus-neutralizing antibody titers directed against VP2 and perhaps by cellular responses to NS1 and NS2. T lymphocyte responses were cross-reactive between BTV-2 and BTV-8, suggesting that NS1 and NS2 may provide the basis of an adaptable vaccine that can be varied by using VP2 of different serotypes. The detection of different levels of VP7 antibodies in vaccinated animals and controls after challenge suggested a compliancy between the vaccine and the DIVA companion test. This BTV subunit vaccine is a promising candidate that should be further evaluated and developed to protect against different serotypes.
authors.affiliation: Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Department of Clinical Sciences, Almas allé 4 C, Uppsala, Sweden.
authors.forename: Jenna
authors.initials: J
authors.lastname: Anderson
authors.affiliation: Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Department of Clinical Sciences, Almas allé 4 C, Uppsala, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Hägglund
authors.affiliation: ANSES, UMR Virologie 1161 ANSES/INRA/ENVA, 23 Avenue Général de Gaulle, Maisons-Alfort, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bréard
authors.affiliation: INRA, Centre Val de Loire, UE-1277 Plateforme d'Infectiologie expérimentale (PFIE), Route de Crotelles, Nouzilly, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Riou
authors.affiliation: National Veterinary Institute, Department of Virology, Immunology, and Parasitology, Ulls väg 2B, Uppsala, Sweden.
authors.forename: Siamak
authors.initials: S
authors.lastname: Zohari
authors.affiliation: IdVet, 167 rue Mehdi Ben Barka, Montpellier, France.
authors.forename: Loic
authors.initials: L
authors.lastname: Comtet
authors.affiliation: National Veterinary Institute, Department of Virology, Immunology, and Parasitology, Ulls väg 2B, Uppsala, Sweden.
authors.forename: Ann-Sophie
authors.initials: AS
authors.lastname: Olofson
authors.affiliation: INRA, Centre Val de Loire, UE-1277 Plateforme d'Infectiologie expérimentale (PFIE), Route de Crotelles, Nouzilly, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Gélineau
authors.affiliation: INRA, Centre Val de Loire, UE-1277 Plateforme d'Infectiologie expérimentale (PFIE), Route de Crotelles, Nouzilly, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Martin
authors.affiliation: National Veterinary Institute, Department of Virology, Immunology, and Parasitology, Ulls väg 2B, Uppsala, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: Elvander
authors.affiliation: National Veterinary Institute, Department of Virology, Immunology, and Parasitology, Ulls väg 2B, Uppsala, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Blomqvist
authors.affiliation: ANSES, UMR Virologie 1161 ANSES/INRA/ENVA, 23 Avenue Général de Gaulle, Maisons-Alfort, France.
authors.forename: Stéphan
authors.initials: S
authors.lastname: Zientara
authors.affiliation: Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Department of Clinical Sciences, Almas allé 4 C, Uppsala, Sweden; National Veterinary Institute, Department of Virology, Immunology, and Parasitology, Ulls väg 2B, Uppsala, Sweden. Electronic address: jean-francois.valarcher@slu.se.
authors.forename: Jean Francois
authors.initials: JF
authors.lastname: Valarcher
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001819:Bluetongue / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001820:Bluetongue virus / Q000145:classification / Q000276:immunology*; D002417:Cattle; D002784:Cholesterol / Q000008:administration & dosage; D004338:Drug Combinations; D005260:Female; D007279:Injections, Subcutaneous; D010743:Phospholipids / Q000008:administration & dosage; D012503:Saponins / Q000008:administration & dosage; D065288:Serogroup; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014766:Viremia / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004338:Drug Combinations; C493786:ISCOMATRIX; D010743:Phospholipids; D012503:Saponins; D022223:Vaccines, Subunit; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines; D002784:Cholesterol
keywords: Bluetongue virus serotype 8; Cattle; DIVA; Protection; Subunit; Vaccine