Microspheres-prime/rMVA-boost vaccination enhances humoral and cellular immune response in IFNAR(-/-) mice conferring protection against serotypes 1 and 4 of bluetongue virus.
Bluetongue virus (BTV) is the causative agent of bluetongue disease (BT), which affects domestic and wild ruminants. At the present, 27 different serotypes have been documented. Vaccination has been demonstrated as one of the most effective methods to avoid viral dissemination. To overcome the drawbacks associated with the use of inactivated and attenuated vaccines we engineered a new recombinant BTV vaccine candidate based on proteins VP2, VP7, and NS1 of BTV-4 that were incorporated into avian reovirus muNS-Mi microspheres (MS-VP2/VP7/NS1) and recombinant modified vaccinia virus Ankara (rMVA). The combination of these two antigen delivery systems in a heterologous prime-boost vaccination strategy generated significant levels of neutralizing antibodies in IFNAR(-/-) mice. Furthermore, this immunization strategy increased the ratio of IgG2a/IgG1 in sera, indicating an induction of a Th1 response, and elicited a CD8 T cell response. Immunized mice were protected against lethal challenges with the homologous serotype 4 and the heterologous serotype 1 of BTV. All these results support the strategy based on microspheres in combination with rMVAs as a promising multiserotype vaccine candidate against BTV.
Centro de Investigación en Sanidad Animal, INIA-CISA, Valdeolmos, Madrid, Spain.
Alejandro
A
Marín-López
Centro de Investigación en Sanidad Animal, INIA-CISA, Valdeolmos, Madrid, Spain.
Eva
E
Calvo-Pinilla
Centro de Investigación en Sanidad Animal, INIA-CISA, Valdeolmos, Madrid, Spain.
Diego
D
Barriales
Centro de Investigación en Sanidad Animal, INIA-CISA, Valdeolmos, Madrid, Spain.
Gema
G
Lorenzo
Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS) and Departamento de Bioquímica e Bioloxía Molecular, Universidade de Santiago de Compostela, Spain.
Javier
J
Benavente
Centro de Investigación en Sanidad Animal, INIA-CISA, Valdeolmos, Madrid, Spain.
Alejandro
A
Brun
Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS) and Departamento de Bioquímica e Bioloxía Molecular, Universidade de Santiago de Compostela, Spain.
Jose Manuel
JM
Martínez-Costas
Centro de Investigación en Sanidad Animal, INIA-CISA, Valdeolmos, Madrid, Spain. Electronic address: ortego@inia.es.
Javier
J
Ortego
D000818:Animals; D057134:Antibodies, Neutralizing; D001819:Bluetongue / Q000517:prevention & control*; D001820:Bluetongue virus / Q000145:classification / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D007111:Immunity, Cellular / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology*; D007114:Immunization; D007117:Immunization, Secondary / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008863:Microspheres; D030101:Orthoreovirus, Avian / Q000235:genetics / Q000276:immunology; D053633:Receptor, Interferon alpha-beta / Q000276:immunology*; D065288:Serogroup; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*; D014709:Vero Cells; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
D057134:Antibodies, Neutralizing; D036022:Capsid Proteins; D007074:Immunoglobulin G; D052118:Lysosomal-Associated Membrane Protein 1; C078966:NS1 protein, bluetongue virus; C442520:VP2 protein, Bluetongue virus; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines; C066862:VP7 protein, orbivirus; D053633:Receptor, Interferon alpha-beta
Bluetongue; MVA; Microspheres; Multiserotype; Vaccine