The MVA-VP2-NS1-2A-NS2-Nt vaccine candidate provides heterologous protection in sheep against bluetongue virus
Bluetongue (BT) is an important arthropod-borne livestock disease transmitted by Culicoides midges. The etiological agent, Bluetongue virus (BTV), can lead to severe economic losses due to reduced productivity and trade restrictions. Nowadays, classical vaccines based on inactivated viruses are used...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1566225/full |
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| author | Luis Jiménez-Cabello Luis Jiménez-Cabello Sergio Utrilla-Trigo Miguel Illescas-Amo Karen Rodríguez-Sabando Julio Benavides-Silván Eva Calvo-Pinilla Javier Ortego |
| author_facet | Luis Jiménez-Cabello Luis Jiménez-Cabello Sergio Utrilla-Trigo Miguel Illescas-Amo Karen Rodríguez-Sabando Julio Benavides-Silván Eva Calvo-Pinilla Javier Ortego |
| author_sort | Luis Jiménez-Cabello |
| collection | DOAJ |
| description | Bluetongue (BT) is an important arthropod-borne livestock disease transmitted by Culicoides midges. The etiological agent, Bluetongue virus (BTV), can lead to severe economic losses due to reduced productivity and trade restrictions. Nowadays, classical vaccines based on inactivated viruses are used to control outbreaks but do not confer multiserotype protection, which reinforces the idea of pursuing research into developing strategies that enhance the immune response directed to conserved antigenic regions, aiming broader protection across multiple serotypes. Recently, we described a vaccine candidate that confers full protection against a homologous serotype of BTV based on recombinant Modified Vaccinia Virus Ankara (MVA) co-expressing the highly conserved BTV nonstructural protein NS1 and the N-terminal end of NS2 along with protein VP2 of BTV-4. In this work, we evaluated the multiserotype protective capacity of this recombinant vaccine candidate in sheep after infection with the heterologous virus BTV-8, achieving a significant blockade of viral replication and attenuation of the clinical signs induced by BTV. After infection, vaccinated animals showed more regulated pro-inflammatory cytokine levels compared to non-vaccinated sheep. In addition, we noticed the induction of potent T cell immune responses specific to NS1 and NS2-Nt proteins of BTV, mainly based on CD8+ T cells, which could mediate the protection against BTV-8. Moreover, stimulated immunized sheep PBMCs with BTV antigens triggered the secretion of IL-6, IL-1β, IL-1α, IL-17a, IL-10 and IFN-γ, cytokines that play crucial roles in initiating immune responses. |
| format | Article |
| id | doaj-art-c2ce0b68d2c8473a9cc1ca82c821fade |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-c2ce0b68d2c8473a9cc1ca82c821fade2025-08-20T03:52:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15662251566225The MVA-VP2-NS1-2A-NS2-Nt vaccine candidate provides heterologous protection in sheep against bluetongue virusLuis Jiménez-Cabello0Luis Jiménez-Cabello1Sergio Utrilla-Trigo2Miguel Illescas-Amo3Karen Rodríguez-Sabando4Julio Benavides-Silván5Eva Calvo-Pinilla6Javier Ortego7Centro de Investigación en Sanidad Animal (CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Valdeolmos, Madrid, SpainUniversidad Autónoma de Madrid (UAM), Escuela de doctorado, Madrid, SpainCentro de Investigación en Sanidad Animal (CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Valdeolmos, Madrid, SpainCentro de Investigación en Sanidad Animal (CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Valdeolmos, Madrid, SpainCentro de Investigación en Sanidad Animal (CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Valdeolmos, Madrid, SpainInstituto de Ganadería de Montaña (CSIC-Universidad de León), León, SpainCentro de Investigación en Sanidad Animal (CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Valdeolmos, Madrid, SpainCentro de Investigación en Sanidad Animal (CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Valdeolmos, Madrid, SpainBluetongue (BT) is an important arthropod-borne livestock disease transmitted by Culicoides midges. The etiological agent, Bluetongue virus (BTV), can lead to severe economic losses due to reduced productivity and trade restrictions. Nowadays, classical vaccines based on inactivated viruses are used to control outbreaks but do not confer multiserotype protection, which reinforces the idea of pursuing research into developing strategies that enhance the immune response directed to conserved antigenic regions, aiming broader protection across multiple serotypes. Recently, we described a vaccine candidate that confers full protection against a homologous serotype of BTV based on recombinant Modified Vaccinia Virus Ankara (MVA) co-expressing the highly conserved BTV nonstructural protein NS1 and the N-terminal end of NS2 along with protein VP2 of BTV-4. In this work, we evaluated the multiserotype protective capacity of this recombinant vaccine candidate in sheep after infection with the heterologous virus BTV-8, achieving a significant blockade of viral replication and attenuation of the clinical signs induced by BTV. After infection, vaccinated animals showed more regulated pro-inflammatory cytokine levels compared to non-vaccinated sheep. In addition, we noticed the induction of potent T cell immune responses specific to NS1 and NS2-Nt proteins of BTV, mainly based on CD8+ T cells, which could mediate the protection against BTV-8. Moreover, stimulated immunized sheep PBMCs with BTV antigens triggered the secretion of IL-6, IL-1β, IL-1α, IL-17a, IL-10 and IFN-γ, cytokines that play crucial roles in initiating immune responses.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1566225/fullbluetongue virus (BTV)orbivirusvaccineMVADIVAmultiserotype |
| spellingShingle | Luis Jiménez-Cabello Luis Jiménez-Cabello Sergio Utrilla-Trigo Miguel Illescas-Amo Karen Rodríguez-Sabando Julio Benavides-Silván Eva Calvo-Pinilla Javier Ortego The MVA-VP2-NS1-2A-NS2-Nt vaccine candidate provides heterologous protection in sheep against bluetongue virus Frontiers in Immunology bluetongue virus (BTV) orbivirus vaccine MVA DIVA multiserotype |
| title | The MVA-VP2-NS1-2A-NS2-Nt vaccine candidate provides heterologous protection in sheep against bluetongue virus |
| title_full | The MVA-VP2-NS1-2A-NS2-Nt vaccine candidate provides heterologous protection in sheep against bluetongue virus |
| title_fullStr | The MVA-VP2-NS1-2A-NS2-Nt vaccine candidate provides heterologous protection in sheep against bluetongue virus |
| title_full_unstemmed | The MVA-VP2-NS1-2A-NS2-Nt vaccine candidate provides heterologous protection in sheep against bluetongue virus |
| title_short | The MVA-VP2-NS1-2A-NS2-Nt vaccine candidate provides heterologous protection in sheep against bluetongue virus |
| title_sort | mva vp2 ns1 2a ns2 nt vaccine candidate provides heterologous protection in sheep against bluetongue virus |
| topic | bluetongue virus (BTV) orbivirus vaccine MVA DIVA multiserotype |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1566225/full |
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