Cross-protective immune responses against African horse sickness virus after vaccination with protein NS1 delivered by avian reovirus muNS microspheres and modified vaccinia virus Ankara.
Abstract: African horse sickness virus (AHSV) is an insect-borne pathogen that causes acute disease in horses and other equids. In an effort to improve the safety of currently available vaccines and to acquire new knowledge about the determinants of AHSV immunogenicity, new generation vaccines are being developed. In this work we have generated and tested a novel immunization approach comprised of nonstructural protein 1 (NS1) of AHSV serotype 4 (AHSV-4) incorporated into avian reovirus muNS protein microspheres (MS-NS1) and/or expressed using recombinant modified vaccinia virus Ankara vector (MVA-NS1). The protection conferred against AHSV by a homologous MS-NS1 or heterologous MS-NS1 and MVA-NS1 prime/boost was evaluated in IFNAR (-/-) mice. Our results indicate that immunization based on MS-NS1 and MVA-NS1 afforded complete protection against the infection with homologous AHSV-4. Moreover, priming with MS-NS1 and boost vaccination with MVA-NS1 (MS-MVA-NS1) triggered NS1 specific cytotoxic CD8 + T cells and prevented AHSV disease in IFNAR (-/-) mice after challenge with heterologous serotype AHSV-9. Cross-protective immune responses are highly important since AHS can be caused by nine different serotypes, which means that a universal polyvalent vaccination would need to induce protective immunity against all serotypes.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Publication Date: 2019-11-07 PubMed ID: 31708178DOI: 10.1016/j.vaccine.2019.10.087Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research aimed to develop and test a new type of vaccination for the African horse sickness virus (AHSV), which causes acute disease in horses and other equids. Using the nonstructural protein 1 (NS1) of AHSV serotype 4, the researchers developed a vaccination delivered by avian reovirus protein microspheres and/or a modified vaccinia virus Ankara vector. The new approach completely protected against AHSV-4 infection and proved effective at preventing disease after exposure to a different AHSV serotype.
Introduction to African Horse Sickness
- African horse sickness (AHS) is caused by the African horse sickness virus (AHSV), a pathogen carried by insects.
- The disease is acute and affects horses and other equids, causing large fatalities in these animals.
- The virus exists in nine different serotypes, making it difficult to develop a universal vaccine to protect against all types.
Development of a New Vaccine
- To improve the safety and knowledge of vaccines, the researchers developed a new generation of vaccines.
- This involved generating a novel immunization approach that used the nonstructural protein 1 (NS1) of AHSV serotype 4 (AHSV-4).
- The protein was incorporated into avian reovirus muNS protein microspheres (MS-NS1) or expressed using a recombinant modified vaccinia virus Ankara vector (MVA-NS1).
Evaluation of the New Vaccine
- The protection offered by the new vaccine against AHSV was assessed in mice without interferon receptors (IFNAR (-/-) mice).
- Their results revealed that the new MS-NS1 and MVA-NS1-based vaccine could completely protect against AHSV-4 infection.
- Furthermore, the combination of priming with MS-NS1 and then boosting with MVA-NS1 was effective at triggering NS1 specific cytotoxic CD8 + T cells, which marked a major protective immune response against the disease.
Implications of the Research
- The researchers’ vaccination approach also proved protective when the mice were exposed to a different serotype, AHSV-9, signifying the potential for broad-spectrum protection.
- This is highly important, as any effective AHSV vaccine would need to protect against all nine serotypes of the pathogen.
Cite This Article
APA
Marín-López A, Barreiro-Piñeiro N, Utrilla-Trigo S, Barriales D, Benavente J, Nogales A, Martínez-Costas J, Ortego J, Calvo-Pinilla E.
(2019).
Cross-protective immune responses against African horse sickness virus after vaccination with protein NS1 delivered by avian reovirus muNS microspheres and modified vaccinia virus Ankara.
Vaccine, 38(4), 882-889.
https://doi.org/10.1016/j.vaccine.2019.10.087 Publication
Researcher Affiliations
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain.
- Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), and Departamento de Bioquímica e Bioloxía Molecular, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain.
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain.
- Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), and Departamento de Bioquímica e Bioloxía Molecular, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain.
- Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), and Departamento de Bioquímica e Bioloxía Molecular, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain. Electronic address: Lortego@inia.es.
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain.
MeSH Terms
- African Horse Sickness / immunology
- African Horse Sickness / prevention & control
- African Horse Sickness Virus / immunology
- Animals
- Female
- Horses
- Immunity / immunology
- Immunization
- Mice
- Mice, Knockout
- Microspheres
- Orthoreovirus, Avian / immunology
- Receptor, Interferon alpha-beta / genetics
- Serogroup
- Vaccines, Synthetic / immunology
- Vaccinia virus / immunology
- Viral Nonstructural Proteins / immunology
- Viral Vaccines / administration & dosage
- Viral Vaccines / immunology
Citations
This article has been cited 11 times.- Abella-López D, López-Teijeiro A, Pose-Boirazian T, Barreiro-Piñeiro N, Martínez-Costas JM. Nanoencapsulation platform for oral delivery of peptides: In vitro stabilization of AvPAL and formulation of a gastrointestinal-resistant luciferase. Mater Today Bio 2025 Aug;33:101987.
- Calvo-Pinilla E, Moreno S, Barreiro-Piñeiro N, Sánchez-Puig JM, Blasco R, Martínez-Costas J, Brun A, Lorenzo G. Prime-Boost Vaccination Based on Nanospheres and MVA Encoding the Nucleoprotein of Crimean-Congo Hemorrhagic Fever Virus Elicits Broad Immune Responses. Vaccines (Basel) 2025 Mar 10;13(3).
- Calvo-Pinilla E, Jiménez-Cabello L, Utrilla-Trigo S, Illescas-Amo M, Ortego J. Cytokine mRNA Expression Profile in Target Organs of IFNAR (-/-) Mice Infected with African Horse Sickness Virus. Int J Mol Sci 2024 Feb 8;25(4).
- Utrilla-Trigo S, Jiménez-Cabello L, Marín-López A, Illescas-Amo M, Andrés G, Calvo-Pinilla E, Lorenzo G, van Rijn PA, Ortego J, Nogales A. Engineering recombinant replication-competent bluetongue viruses expressing reporter genes for in vitro and non-invasive in vivo studies. Microbiol Spectr 2024 Mar 5;12(3):e0249323.
- Orlova OV, Glazkova DV, Bogoslovskaya EV, Shipulin GA, Yudin SM. Development of Modified Vaccinia Virus Ankara-Based Vaccines: Advantages and Applications. Vaccines (Basel) 2022 Sep 13;10(9).
- Jiménez-Cabello L, Utrilla-Trigo S, Barreiro-Piñeiro N, Pose-Boirazian T, Martínez-Costas J, Marín-López A, Ortego J. Nanoparticle- and Microparticle-Based Vaccines against Orbiviruses of Veterinary Importance. Vaccines (Basel) 2022 Jul 14;10(7).
- Marín-López A, Utrilla-Trigo S, Jiménez-Cabello L, Ortego J. Recombinant Modified Vaccinia Virus Ankara Development to Express VP2, NS1, and VP7 Proteins of Bluetongue Virus. Methods Mol Biol 2022;2465:177-193.
- Pose-Boirazian T, Eibes G, Barreiro-Piñeiro N, Díaz-Jullien C, Lema JM, Martínez-Costas J. Chemical and thermal stabilization of CotA laccase via a novel one-step expression and immobilization in muNS-Mi nanospheres. Sci Rep 2021 Feb 2;11(1):2802.
- Jiménez-Cabello L, Utrilla-Trigo S, Calvo-Pinilla E, Moreno S, Nogales A, Ortego J, Marín-López A. Viral Vector Vaccines against Bluetongue Virus. Microorganisms 2020 Dec 25;9(1).
- Calvo-Pinilla E, Marín-López A, Moreno S, Lorenzo G, Utrilla-Trigo S, Jiménez-Cabello L, Benavides J, Nogales A, Blasco R, Brun A, Ortego J. A protective bivalent vaccine against Rift Valley fever and bluetongue. NPJ Vaccines 2020;5(1):70.
- Calvo-Pinilla E, Marín-López A, Utrilla-Trigo S, Jiménez-Cabello L, Ortego J. Reverse genetics approaches: a novel strategy for African horse sickness virus vaccine design. Curr Opin Virol 2020 Oct;44:49-56.
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