Bluetongue virus without NS3/NS3a expression is not virulent and protects against virulent bluetongue virus challenge
Autor: | Eline Verheij, Piet A. van Rijn, Femke Feenstra, René G. P. van Gennip, Mieke A. Maris-Veldhuis |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
ns3
sheep viruses Virulence serotype 8 Viral Nonstructural Proteins Antibodies Viral Bluetongue Virus Microbiology Cell Line Gene Knockout Techniques Virology Cricetinae Animals antibodies Viremia rna segment particles NS3 Attenuated vaccine biology Viral Core Proteins Vaccination Outbreak Viral Vaccines differentiation Culicoides biology.organism_classification Antibodies Neutralizing Virology & Molecular Biology Virologie & Moleculaire Biologie cattle biology.protein vaccinated animals Capsid Proteins Female Antibody europe Bluetongue virus |
Zdroj: | Journal of General Virology 95 (2014) Pt. 9 Journal of General Virology, 95(Pt. 9), 2019-2029 |
ISSN: | 0022-1317 2019-2029 |
Popis: | Bluetongue is a disease in ruminants caused by the bluetongue virus (BTV), and is spread by Culicoides biting midges. Bluetongue outbreaks cause huge economic losses and death in sheep in several parts of the world. The most effective measure to control BTV is vaccination. However, both commercially available vaccines and recently developed vaccine candidates have several shortcomings. Therefore, we generated and tested next-generation vaccines for bluetongue based on the backbone of a laboratory-adapted strain of BTV-1, avirulent BTV-6 or virulent BTV-8. All vaccine candidates were serotyped with VP2 of BTV-8 and did not express NS3/NS3a non-structural proteins, due to induced deletions in the NS3/NS3a ORF. Sheep were vaccinated once with one of these vaccine candidates and were challenged with virulent BTV-8 3 weeks after vaccination. The NS3/NS3a knockout mutation caused complete avirulence for all three BTV backbones, including for virulent BTV-8, indicating that safety is associated with the NS3/NS3a knockout phenotype. Viraemia of vaccine virus was not detected using sensitive PCR diagnostics. Apparently, the vaccine viruses replicated only locally, which will minimize spread by the insect vector. In particular, the vaccine based on the BTV-6 backbone protected against disease and prevented viraemia of challenge virus, showing the efficacy of this vaccine candidate. The lack of NS3/NS3a expression potentially enables the differentiation of infected from vaccinated animals, which is important for monitoring virus spread in vaccinated livestock. The disabled infectious single-animal vaccine for bluetongue presented here is very promising and will be the subject of future studies. |
Databáze: | OpenAIRE |
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