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Open AccessArticle

Heterologous Combination of ChAdOx1 and MVA Vectors Expressing Protein NS1 as Vaccination Strategy to Induce Durable and Cross-Protective CD8+ T Cell Immunity to Bluetongue Virus

1
Centro de Investigación en Sanidad Animal (CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Valdeolmos, 28130 Madrid, Spain
2
Instituto de Ganadería de Montaña (CSIC-Universidad de León), 24346 León, Spain
3
The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
*
Author to whom correspondence should be addressed.
Present address: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06519, USA
Vaccines 2020, 8(3), 346; https://doi.org/10.3390/vaccines8030346
Received: 2 June 2020 / Revised: 24 June 2020 / Accepted: 27 June 2020 / Published: 29 June 2020
(This article belongs to the Special Issue Development of Cross-Protective Vaccines)
The sequence of non-structural protein NS1 of bluetongue virus (BTV), which contains immunodominant CD8+ T cell epitopes, is highly conserved among BTV serotypes, and has therefore become a major tool in the development of a universal BTV vaccine. In this work, we have engineered multiserotype BTV vaccine candidates based on recombinant chimpanzee adenovirus (ChAdOx1) and modified vaccinia virus Ankara (MVA) vectors expressing the NS1 protein of BTV-4 or its truncated form NS1-Nt. A single dose of ChAdOx1-NS1 or ChAdOx1-NS1-Nt induced a moderate CD8+ T cell response and protected IFNAR(-/-) mice against a lethal dose of BTV-4/MOR09, a reassortant strain between BTV-1 and BTV-4, although the animals showed low viremia after infection. Furthermore, IFNAR(-/-) mice immunized with a single dose of ChAdOx1-NS1 were protected after challenge with a lethal dose of BTV-8 in absence of viremia nor clinical signs. Additionally, the heterologous prime-boost ChAdOx1/MVA expressing NS1 or NS1-Nt elicited a robust NS1 specific CD8+ T cell response and protected the animals against BTV-4/MOR09 even 16 weeks after immunization, with undetectable levels of viremia at any time after challenge. Subsequently, the best immunization strategy based on ChAdOx1/MVA-NS1 was assayed in sheep. Non-immunized animals presented fever and viremia levels up to 104 PFU/mL after infection. In contrast, although viremia was detected in immunized sheep, the level of virus in blood was 100 times lower than in non-immunized animals in absence of clinical signs. View Full-Text
Keywords: bluetongue virus (BTV); modified vaccinia Ankara (MVA); Chimpanzee adenovirus (ChAdOx1), vaccine; cellular response; protein NS1 bluetongue virus (BTV); modified vaccinia Ankara (MVA); Chimpanzee adenovirus (ChAdOx1), vaccine; cellular response; protein NS1
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Utrilla-Trigo, S.; Jiménez-Cabello, L.; Alonso-Ravelo, R.; Calvo-Pinilla, E.; Marín-López, A.; Moreno, S.; Lorenzo, G.; Benavides, J.; Gilbert, S.; Nogales, A.; Ortego, J. Heterologous Combination of ChAdOx1 and MVA Vectors Expressing Protein NS1 as Vaccination Strategy to Induce Durable and Cross-Protective CD8+ T Cell Immunity to Bluetongue Virus. Vaccines 2020, 8, 346.

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