title: Immunisation with bacterial expressed VP2 and VP5 of bluetongue virus (BTV) protect α/β interferon-receptor knock-out (IFNAR(-/-)) mice from homologous lethal challenge.
abstract: BTV-4 structural proteins VP2 (as two domains: VP2D1 and VP2D2), VP5 (lacking the first 100 amino acids: VP5Δ1-100) and full-length VP7, expressed in bacteria as soluble glutathione S-transferase (GST) fusion-proteins, were used to immunise Balb/c and α/β interferon receptor knock-out (IFNAR(-/-)) mice. Neutralising antibody (NAbs) titres (expressed as log10 of the reciprocal of the last dilution of mouse serum which reduced plaque number by ≥50%) induced by the VP2 domains ranged from 1.806 to 2.408 in Balb/c and IFNAR(-/-) mice. The immunised IFNAR(-/-) mice challenged with a homologous live BTV-4 survived and failed to develop signs of infection (ocular discharge and apathy). Although subsequent attempts to isolate virus were unsuccessful (possibly reflecting presence of neutralising antibodies), a transient/low level viraemia was detected by real time RT-PCR. In contrast, mice immunised with the two VP2 domains with or without VP5Δ1-100 and VP7, then challenged with the heterologous serotype, BTV-8, all died by day 7 post-infection. We conclude that immunisation with bacterially-expressed VP2 domains can induce strong serotype-specific NAb responses. Bacterial expression could represent a cost effective and risk-free alternative to the use of live or inactivated vaccines, particularly if viruses prove to be difficult to propagate in cell culture (like BTV-25). A vaccine based on bacterially expressed VP2 and VP5 of BTV is also DIVA-compatible.
authors.affiliation: Vector-borne Viral Diseases Programme, The Pirbright Institute, Pirbright, Woking, Surrey GU240NF, United Kingdom.
authors.forename: Fauziah
authors.initials: F
authors.lastname: Mohd Jaafar
authors.affiliation: Vector-borne Viral Diseases Programme, The Pirbright Institute, Pirbright, Woking, Surrey GU240NF, United Kingdom.
authors.forename: Mourad
authors.initials: M
authors.lastname: Belhouchet
authors.affiliation: Anses, INRA, ENVA-UPEC, UMR 1161 Virology Unit, French Agency for Food, Environmental and Occupational Health and Safety, Maisons-Alfort, 94703 France.
authors.forename: Damien
authors.initials: D
authors.lastname: Vitour
authors.affiliation: Anses, INRA, ENVA-UPEC, UMR 1161 Virology Unit, French Agency for Food, Environmental and Occupational Health and Safety, Maisons-Alfort, 94703 France.
authors.forename: Micheline
authors.initials: M
authors.lastname: Adam
authors.affiliation: Anses, INRA, ENVA-UPEC, UMR 1161 Virology Unit, French Agency for Food, Environmental and Occupational Health and Safety, Maisons-Alfort, 94703 France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Breard
authors.affiliation: Anses, INRA, ENVA-UPEC, UMR 1161 Virology Unit, French Agency for Food, Environmental and Occupational Health and Safety, Maisons-Alfort, 94703 France.
authors.forename: Stéphan
authors.initials: S
authors.lastname: Zientara
authors.affiliation: Vector-borne Viral Diseases Programme, The Pirbright Institute, Pirbright, Woking, Surrey GU240NF, United Kingdom.
authors.forename: Peter P C
authors.initials: PP
authors.lastname: Mertens
authors.affiliation: Vector-borne Viral Diseases Programme, The Pirbright Institute, Pirbright, Woking, Surrey GU240NF, United Kingdom. Electronic address: houssam.attoui@pirbright.ac.uk.
authors.forename: Houssam
authors.initials: H
authors.lastname: Attoui
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001819:Bluetongue / Q000517:prevention & control*; D036022:Capsid Proteins / Q000276:immunology*; D005260:Female; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000235:genetics*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; C442520:VP2 protein, Bluetongue virus; C488468:VP5 protein, Bluetongue virus; D014765:Viral Vaccines; D053633:Receptor, Interferon alpha-beta
keywords: Balb/c and IFNAR(−/−) mice; Bluetongue virus; Capsid subunit vaccine; Neutralising antibodies; Orbivirus