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Characterisation of vaccine-induced, broadly cross-reactive IFN-gamma secreting T cell responses that correlate with rapid protection against classical swine fever virus

机译:疫苗诱导的广泛交叉反应性IFN-γ分泌性T细胞反应的表征,与快速抵抗经典猪瘟病毒有关

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Live attenuated C-strain classical swine fever viruses (CSFV) provide a rapid onset of protection, but the lack of a serological test that can differentiate vaccinated from infected animals limits their application in CSF outbreaks. Since immunity may precede antibody responses, we examined the kinetics and specificity of peripheral blood T cell responses from pigs vaccinated with a C-strain vaccine and challenged after five days with a genotypically divergent CSFV isolate. Vaccinated animals displayed virus-specific IFN-gamma responses from day 3 post-challenge, whereas, unvaccinated challenge control animals failed to mount a detectable response. Both CD4(+) and cytotoxic CD8(+) T cells were identified as the cellular source of IFN-gamma. IFN-gamma responses showed extensive cross-reactivity when T cells were stimulated with CSFV isolates spanning the major genotypes. To determine the specificity of these responses, T cells were stimulated with recombinant CSFV proteins and a proteome-wide peptide library from a related virus, BVDV. Major cross-reactive peptides were mapped on the E2 and NS3 proteins. Finally, IFN-gamma was shown to exert potent antiviral effects on CSFV in vitro. These data support the involvement of broadly cross-reactive T cell IFN-gamma responses in the rapid protection conferred by the C-strain vaccine and this information should aid the development of the next generation of CSFV vaccines. Crown Copyright (c) 2012 Published by Elsevier Ltd
机译:减毒的C株经典猪瘟病毒(CSFV)可以提供快速的保护作用,但是缺乏能够区分接种疫苗的动物与感染动物的血清学检测方法,限制了它们在CSF爆发中的应用。由于免疫可能先于抗体反应,因此我们检查了接种C株疫苗并经基因型不同的CSFV分离株攻击5天后的猪外周血T细胞反应的动力学和特异性。从攻击后第3天起,接种疫苗的动物表现出病毒特异性IFN-γ反应,而未接种疫苗的攻击对照动物未能产生可检测到的反应。 CD4(+)和细胞毒性CD8(+)T细胞均被确定为IFN-γ的细胞来源。当用跨越主要基因型的CSFV分离株刺激T细胞时,IFN-γ反应显示出广泛的交叉反应性。为了确定这些反应的特异性,用重组CSFV蛋白和来自相关病毒BVDV的整个蛋白质组肽库刺激T细胞。主要的交叉反应肽被定位在E2和NS3蛋白上。最后,IFN-γ在体外对CSFV发挥有效的抗病毒作用。这些数据支持广泛交叉反应的T细胞IFN-γ应答参与C株疫苗赋予的快速保护作用,这一信息应有助于下一代CSFV疫苗的开发。官方版权(c)2012由Elsevier Ltd发布

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