title: VP2, VP7, and NS1 proteins of bluetongue virus targeted in avian reovirus muNS-Mi microspheres elicit a protective immune response in IFNAR(-/-) mice.
abstract: Vaccination is critical for controlling the spread of bluetongue virus (BTV). The inactivated BTV vaccines that are now being used in Europe are effective in preventing outbreaks of BTV but secondary effects associated to repetitive inoculation of aluminum-containing adjuvants and the need to develop safer, cross-reactive, and more efficacious vaccines with differential diagnostic capability have re-stimulated the interest in developing improved vaccination strategies against BTV. We have engineered a subunit BTV vaccine candidate based on proteins VP2, VP7, and NS1 of BTV-4 incorporated into avian reovirus (ARV) muNS-Mi microspheres (MS-VP2/MS-VP7/MS-NS1). IFNAR(-/-) mice immunized with MS-VP2/MS-VP7/MS-NS1 without adjuvant generated significant levels of neutralizing antibodies specific to BTV-4. In addition, vaccination stimulated specific T cell responses, predominantly CD4+, against the virus. Immunized mice were fully protected against a homologous challenge with a lethal dose of BTV-4 and partially cross-protected against a heterologous challenge with a lethal dose of BTV-1. These results support MS-VP2/MS-VP7/MS-NS1 as a promising subunit vaccine candidate against multiple serotypes of BTV as well as the use of microspheres as an alternative delivery method with potent intrinsic adjuvant activity.
authors: Centro de Investigación en Sanidad Animal, INIA-CISA, Valdeolmos, 28130 Madrid, Spain.
authors: Alejandro
authors: A
authors: Marín-López
authors: Centro Singular de Investigación en Química Biológica y Materiales Moleculares (CIQUS), Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors: Iria
authors: I
authors: Otero-Romero
authors: Centro de Investigación en Sanidad Animal, INIA-CISA, Valdeolmos, 28130 Madrid, Spain.
authors: Francisco
authors: F
authors: de la Poza
authors: Centro Singular de Investigación en Química Biológica y Materiales Moleculares (CIQUS), Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors: Rebeca
authors: R
authors: Menaya-Vargas
authors: Centro de Investigación en Sanidad Animal, INIA-CISA, Valdeolmos, 28130 Madrid, Spain.
authors: Eva
authors: E
authors: Calvo-Pinilla
authors: Centro Singular de Investigación en Química Biológica y Materiales Moleculares (CIQUS), Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors: Javier
authors: J
authors: Benavente
authors: Centro Singular de Investigación en Química Biológica y Materiales Moleculares (CIQUS), Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors: José M
authors: JM
authors: Martínez-Costas
authors: Centro de Investigación en Sanidad Animal, INIA-CISA, Valdeolmos, 28130 Madrid, Spain. Electronic address: ortego@inia.es.
authors: Javier
authors: J
authors: Ortego
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D016367:Baculoviridae / Q000235:genetics; D001819:Bluetongue / Q000276:immunology / Q000517:prevention & control; D001820:Bluetongue virus / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004337:Drug Carriers / Q000627:therapeutic use; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008863:Microspheres; D030101:Orthoreovirus, Avian / Q000235:genetics / Q000276:immunology*; D061987:Sf9 Cells; D012756:Sheep / Q000821:virology; D018411:Spodoptera; D014611:Vaccination; D022223:Vaccines, Subunit / Q000276:immunology; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D004337:Drug Carriers; C078966:NS1 protein, bluetongue virus; C442520:VP2 protein, Bluetongue virus; D022223:Vaccines, Subunit; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines
keywords: Avian reovirus muNS-Mi; Bluetongue virus; IC-tagging; Microspheres; Vaccine