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Increased Clinical Signs and Mortality in IFNAR(−/−) Mice Immunised with the Bluetongue Virus Outer-Capsid Proteins VP2 or VP5, after Challenge with an Attenuated Heterologous Serotype

Attoui, Houssam; Mohd Jaafar, Fauziah; Monsion, Baptiste; Klonjkowski, Bernard; Reid, Elizabeth; Fay, Petra C.; Saunders, Keith; Lomonossoff, George; Haig, David; Mertens, Peter P. C.

Increased Clinical Signs and Mortality in IFNAR(−/−) Mice Immunised with the Bluetongue Virus Outer-Capsid Proteins VP2 or VP5, after Challenge with an Attenuated Heterologous Serotype Thumbnail


Authors

Houssam Attoui

Fauziah Mohd Jaafar

Baptiste Monsion

Bernard Klonjkowski

Elizabeth Reid

Petra C. Fay

Keith Saunders

George Lomonossoff

David Haig



Abstract

Bluetongue is an economically important disease of domesticated and wild ruminants caused by bluetongue virus (BTV). There are at least 36 different serotypes of BTV (the identity of which is determined by its outer-capsid protein VP2), most of which are transmitted by Culicoides biting midges. IFNAR(−/−) mice immunised with plant-expressed outer-capsid protein VP2 (rVP2) of BTV serotypes -1, -4 or -8, or the smaller outer-capsid protein rVP5 of BTV-10, or mock-immunised with PBS, were subsequently challenged with virulent strains of BTV-4 or BTV-8, or with an attenuated clone of BTV-1 (BTV-1RGC7). The mice that had received rVP2 generated a protective immune response against the homologous BTV serotype, reducing viraemia (as detected by qRT-PCR), the severity of clinical signs and mortality levels. No cross-serotype protection was observed after challenge with the heterologous BTV serotypes. However, the severity of clinical signs, viraemia and fatality levels after challenge with the attenuated strain of BTV-1 were all increased in mice immunised with rVP2 of BTV-4 and BTV-8, or with rVP5 of BTV10. The possibility is discussed that non-neutralising antibodies, reflecting serological relationships between the outer-capsid proteins of these different BTV serotypes, could lead to ‘antibody-dependent enhancement of infection’ (ADE). Such interactions could affect the epidemiology and emergence of different BTV strains in the field and would therefore be relevant to the design and implementation of vaccination campaigns.

Citation

Attoui, H., Mohd Jaafar, F., Monsion, B., Klonjkowski, B., Reid, E., Fay, P. C., …Mertens, P. P. C. (2023). Increased Clinical Signs and Mortality in IFNAR(−/−) Mice Immunised with the Bluetongue Virus Outer-Capsid Proteins VP2 or VP5, after Challenge with an Attenuated Heterologous Serotype. Pathogens, 12(4), Article 602. https://doi.org/10.3390/pathogens12040602

Journal Article Type Article
Acceptance Date Apr 13, 2023
Online Publication Date Apr 15, 2023
Publication Date 2023-04
Deposit Date Apr 18, 2023
Publicly Available Date Apr 19, 2023
Journal Pathogens
Publisher MDPI AG
Peer Reviewed Peer Reviewed
Volume 12
Issue 4
Article Number 602
DOI https://doi.org/10.3390/pathogens12040602
Keywords Bluetongue virus (BTV); vaccination; VP2; VP5; heterologous serotype challenge
Public URL https://nottingham-repository.worktribe.com/output/19760748
Publisher URL https://www.mdpi.com/2076-0817/12/4/602

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