title: Immunization of knock-out α/β interferon receptor mice against lethal bluetongue infection with a BoHV-4-based vector expressing BTV-8 VP2 antigen.
abstract: New effective tools for vaccine strategies are necessary to limit the spread of bluetongue, an insect-transmitted viral disease of domestic and wild ruminants. In the present study, BoHV-4-based vector cloned as a bacterial artificial chromosome (BAC) was engineered to express the bluetongue virus (BTV) immune-dominant glycoprotein VP2 provided of a heterologous signal peptide to its amino terminal and a trans-membrane domain to its carboxyl terminal (IgK-VP2gDtm), to allow the VP2 expression targeting to the cell membrane fraction. Based on adult α/β interferon receptor knockout (IFNAR(-/-)) mice, a newly generated bluetongue laboratory animal model, a pre-challenge experiment was performed to test BoHV-4 safety on such immune-compromised animal. BoHV-4 infected IFNAR(-/-) mice did not show clinical signs even following the inoculation of BoHV-4 intra-cerebrally, although many areas of the brain got transduced. IFNAR(-/-) mice intraperitoneally inoculated twice with BoHV-4-A-IgK-VP2gDtm at different time points developed serum neutralizing antibodies against BTV and showed a strongly reduced viremia and a longer survival time when challenged with a lethal dose of BTV-8. The data acquired in this pilot study validate BoHV-4-based vector as a safe and effective heterologous antigen carrier/producer for the formulation of enhanced recombinant immunogens for the vaccination against lethal bluetongue.
authors.affiliation: Dipartimento di Salute Animale, Facoltà di Medicina Veterinaria, Università di Parma, via del Taglio 10, 43100 Parma, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Franceschi
authors.forename: Antonio
authors.initials: A
authors.lastname: Capocefalo
authors.forename: Eva
authors.initials: E
authors.lastname: Calvo-Pinilla
authors.forename: Marco
authors.initials: M
authors.lastname: Redaelli
authors.forename: Carla
authors.initials: C
authors.lastname: Mucignat-Caretta
authors.forename: Peter
authors.initials: P
authors.lastname: Mertens
authors.forename: Javier
authors.initials: J
authors.lastname: Ortego
authors.forename: Gaetano
authors.initials: G
authors.lastname: Donofrio
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000097:blood; D001483:Base Sequence; D001819:Bluetongue / Q000276:immunology / Q000517:prevention & control*; D001820:Bluetongue virus / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004285:Dogs; D005822:Genetic Vectors; D026021:Herpesvirus 4, Bovine / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010865:Pilot Projects; D053633:Receptor, Interferon alpha-beta / Q000235:genetics*; D010948:Viral Plaque Assay; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*; D014766:Viremia / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; C442520:VP2 protein, Bluetongue virus; D014765:Viral Vaccines; D053633:Receptor, Interferon alpha-beta