Abstract
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.
Highlights
Bluetongue is a vector-borne viral disease that affects both domestic and wild ruminants and is characterized by vascular injury resulting in tissue necrosis, hemorrhage and edema, among other lesions [1]
In order to evaluate the expression of NS1 and NS1-Nt of bluetongue virus (BTV)-4 from ChAdOx1 and modified vaccinia virus Ankara (MVA) vectors in infected HEK-293 and DF-1 cells, respectively, immunofluorescence assays were performed
The typical punctuated signal for NS1 and NS1-Nt was observed in HEK-293 cells infected with ChAdOx-NS1 (Figure 2b) and ChAdOx-NS1-Nt (Figure 2c) Expression of the NS1 and NS1-Nt BTV proteins was observed in DF-1 cells infected with MVA-NS1 (Figure 2e) and MVA-NS1-Nt (Figure 2f)
Summary
Bluetongue is a vector-borne viral disease that affects both domestic and wild ruminants and is characterized by vascular injury resulting in tissue necrosis, hemorrhage and edema, among other lesions [1]. This disease is caused by bluetongue virus (BTV), one of the most important livestock. Vaccines 2020, 8, 346 pathogens worldwide [2] This non-enveloped virus that belongs to the genus Orbivirus within the family Reoviridae is characterized by its icosahedral layered capsid. Serotypes BTV-28 and BTV-29, which are closely related to other typical BTV serotypes, have recently been described, and two others are being studied [4,12,13]
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