RT Journal Article
T1 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
A1 Utrilla Trigo, Sergio
A1 Jiménez Cabello, Luis
A1 Alonso Ravelo, Ruymán
A1 Calvo Pinilla, Eva
A1 Marín López, Alejandro
A1 Moreno, Sandra
A1 Lorenzo, Gema
A1 Benavides, Julio
A1 Gilbert, Sarah
A1 Nogales, Aitor
A1 Ortego, Javier
AB 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.
PB MDPI
SN 2076-393X
YR 2020
FD 2020-06-29
LK https://hdl.handle.net/20.500.14352/8344
UL https://hdl.handle.net/20.500.14352/8344
LA eng
NO Unión Europea. Horizonte 2020
NO Ministerio de Ciencia e Innovación (MICINN)
NO Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal
DS Docta Complutense
RD 9 abr 2025