Characterisation of vaccine-induced, broadly cross-reactive IFN-γ secreting T cell responses that correlate with rapid protection against classical swine fever virus
Characterisation of vaccine-induced, broadly cross-reactive IFN-γ secreting T cell responses that correlate with rapid protection against classical swine fever virus
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DOI：
10.1016/j.vaccine.2012.02.029
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发表时间：
2012-04-05
期刊：
影响因子：
5.5
通讯作者：
Crooke, Helen R.
中科院分区：
文献类型：
--
作者：
Graham, Simon P.;Haines, Felicity J.;Crooke, Helen R.
减毒活C株猪瘟病毒（CSFV）提供了一种快速的保护作用，但缺乏血清学试验，可以区分接种疫苗的感染动物限制了它们在CSF爆发的应用。由于免疫可能先于抗体应答，我们研究了用C株疫苗接种的猪的外周血T细胞应答的动力学和特异性，并在5天后用基因型不同的CSFV分离株进行攻击。接种疫苗的动物从攻毒后第3天开始显示病毒特异性IFN-γ应答，而未接种疫苗的攻毒对照动物未能产生可检测的应答。CD 4（+）和细胞毒性CD 8（+）T细胞均被鉴定为IFN-γ的细胞来源。IFN-γ反应显示出广泛的交叉反应性时，T细胞刺激CSFV分离跨越主要基因型。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的蛋白质组范围肽文库刺激T细胞。主要的交叉反应肽被映射到E2和NS 3蛋白上。最后，IFN-γ在体外显示出对CSFV发挥有效的抗病毒作用。这些数据支持广泛交叉反应性T细胞IFN-γ应答参与C株疫苗赋予的快速保护，并且这些信息应有助于下一代CSFV疫苗的开发。皇冠版权所有（c）2012由爱思唯尔有限公司出版。保留所有权利。
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. All rights reserved.