title: Enhanced neutralising antibody response to bovine viral diarrhoea virus (BVDV) induced by DNA vaccination in calves.
abstract: DNA vaccination is effective in inducing potent immunity in mice; however it appears to be less so in large animals. Increasing the dose of DNA plasmid to activate innate immunity has been shown to improve DNA vaccine adaptive immunity. Retinoic acid-inducible gene I (RIG-I) is a critical cytoplasmic double-stranded RNA pattern receptor required for innate immune activation in response to viral infection. RIG-I recognise viral RNA and trigger antiviral response, resulting in type I interferon (IFN) and inflammatory cytokine production. In an attempt to enhance the antibody response induced by BVDV DNA in cattle, we expressed BVDV truncated E2 (E2t) and NS3 codon optimised antigens from antibiotic free-plasmid vectors expressing a RIG-I agonist and designated either NTC E2t(co) and NTC NS3(co). To evaluate vaccine efficacy, groups of five BVDV-free calves were intramuscularly injected three times with NTC E2t(co) and NTC NS3(co) vaccine plasmids individually or in combination. Animals vaccinated with our (previously published) conventional DNA vaccines pSecTag/E2 and pTriExNS3 and plasmids expressing RIG-I agonist only presented both the positive and mock-vaccine groups. Our results showed that vaccines coexpressing E2t with a RIG-I agonist induced significantly higher E2 antigen specific antibody response (p<0.05). Additionally, E2t augmented the immune response to NS3 when the two vaccines were delivered in combination. Despite the lack of complete protection, on challenge day 4/5 calves vaccinated with NTC E2t(co) alone or NTC E2t(co) plus NTC NS3(co) had neutralising antibody titres exceeding 1/240 compared to 1/5 in the mock vaccine control group. Based on our results we conclude that co-expression of a RIG-I agonist with viral antigen could enhance DNA vaccine potency in cattle.
authors.affiliation: Pathology & Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield AL9 7TA, Hertfordshire, UK. Electronic address: lelattar@rvc.ac.uk.
authors.forename: Laila M
authors.initials: LM
authors.lastname: R El-Attar
authors.affiliation: Pathology & Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield AL9 7TA, Hertfordshire, UK.
authors.forename: Carole
authors.initials: C
authors.lastname: Thomas
authors.affiliation: Nature Technology Corporation, 4701 Innovation Drive, Lincoln, NE 68521, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Luke
authors.affiliation: Nature Technology Corporation, 4701 Innovation Drive, Lincoln, NE 68521, USA.
authors.forename: James
authors.initials: J
authors.lastname: A Williams
authors.affiliation: Pathology & Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield AL9 7TA, Hertfordshire, UK.
authors.forename: Joe
authors.initials: J
authors.lastname: Brownlie
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000517:prevention & control*; D002417:Cattle; D001908:Diarrhea Viruses, Bovine Viral / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D015870:Gene Expression; D005822:Genetic Vectors; D007273:Injections, Intramuscular; D010447:Peptide Hydrolases / Q000235:genetics / Q000276:immunology; D010957:Plasmids; D020365:RNA Helicases / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D010447:Peptide Hydrolases; D020365:RNA Helicases; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines; C076551:gp53, bovine viral diarrhea virus; C086730:p80 protein, bovine viral diarrhea virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
keywords: BVDV marker vaccine; Plasmid DNA vaccine; RIG-I agonist