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Bluetongue virus outer-capsid protein VP2 expressed in Nicotiana Nicotiana benthamiana raises neutralising antibodies and a protective immune response in IFNAR -/- mice

Fay, Petra C.; Attoui, Houssam; Batten, Carrie; Mohd Jaafar, Fauziah; Lomonossoff, George P.; Daly, Janet M.; Mertens, Peter P.C.

Authors

Petra C. Fay

Houssam Attoui

Carrie Batten

Fauziah Mohd Jaafar

George P. Lomonossoff

Janet M. Daly

Peter P.C. Mertens



Abstract

Bluetongue is a severe, economically important disease of ruminants that is widely distributed in tropical and temperate regions around the world. It is associated with major production losses, restrictions of animal movements and trade, as well as costs associated with developing and implementing effective surveillance and control measures. Mammalian hosts infected with bluetongue virus (BTV) generate a protective neutralising antibody response targeting the major BTV outer-capsid protein and serotype-specific antigen, VP2. BTV VP2 proteins that have been expressed in plants are soluble, with a native conformation displaying neutralising epitopes and can assemble with other BTV structural proteins to form virus-like particles (VLPs).

His-tagged VP2 proteins of BTV serotypes 4 and 8 were transiently expressed in Nicotiana benthamiana then purified by immobilised metal affinity chromatography (IMAC). Antisera from IFNAR −/− mice prime/boost vaccinated with the purified proteins, were shown to contain VP2-specific antibodies by Indirect ELISA (I-ELISA), western blotting and serum neutralisation tests (SNT). Vaccinated mice, subsequently challenged with either the homologous or heterologous BTV serotype, developed viraemia by day 3 post-infection. However, no clinical signs were observed in mice challenged with the homologous serotype (either prime-boost or single-shot vaccinated), all of which survived for the duration of the study. In contrast, all of the vaccinated mice challenged with a heterologous serotype, died, showing no evidence of cross-protection or suppression of viraemia, as detected by real-time RT-qPCR or virus isolation. The induction of protective, serotype-specific neutralising antibodies in IFNAR −/− mice, indicates potential for the use of plant-expressed BTV VP2s as subunit vaccine components, or as a basis for serotype-specific serological assays.

Journal Article Type Article
Publication Date Aug 9, 2019
Print ISSN 0264-410X
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 2
Article Number 100026
APA6 Citation Fay, P. C., Attoui, H., Batten, C., Mohd Jaafar, F., Lomonossoff, G. P., Daly, J. M., & Mertens, P. P. (2019). Bluetongue virus outer-capsid protein VP2 expressed in Nicotiana Nicotiana benthamiana raises neutralising antibodies and a protective immune response in IFNAR -/- mice. Vaccine, 2, https://doi.org/10.1016/j.jvacx.2019.100026
DOI https://doi.org/10.1016/j.jvacx.2019.100026
Keywords Bluetongue; BTV; Bluetongue virus; Neutralising antibodies; Subunit protein; VP2; Vaccine; Vaccination; IFNAR
Publisher URL https://www.sciencedirect.com/science/article/pii/S2590136219300270?via%3Dihub

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