Immunisation with BCG and recombinant MVA85A induces long-lasting, polyfunctional Mycobacterium tuberculosis-specific CD4+ memory T lymphocyte populations
Immunisation with BCG and recombinant MVA85A induces long-lasting, polyfunctional Mycobacterium tuberculosis-specific CD4+ memory T lymphocyte populations
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DOI：
10.1002/eji.200737504
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发表时间：
2007-11-01
影响因子：
5.4
通讯作者：
McShane, Helen
中科院分区：
文献类型：
--
作者：
Beveridge, Natalie E. R.;Price, David A.;McShane, Helen
在寻找针对艾滋病毒、结核病和疟疾等细胞内病原体的有效疫苗的过程中，重组病毒载体正越来越多地被用于增强先前启动的T细胞反应。已公布的数据表明，卡介苗-MVA85A(改良痘苗病毒安卡拉表达抗原85A)在人体内具有高度的免疫原性，通过体外干扰素-伽马ELISPOT检测。在这里，我们使用多色流式细胞术更详细地研究了这些疫苗诱导的结核分枝杆菌(M.tb)抗原85A特异性反应的表型和功能特征。有希望的是，抗原85A特异性的CD4(+)T细胞被发现是高度多功能的，可以产生干扰素-γ、肿瘤坏死因子-α、IL-2和MIP-1β。表面染色显示应答的CD4(+)T细胞相对不成熟(CD45RO(+)CD27(Int)CD57(-))；这一观察结果得到了抗原刺激后观察到的强劲增殖反应的支持。此外，这些表型和功能特性与克隆型组成和表位特异性无关，这种特性在疫苗诱导的免疫反应的不同阶段保持不变。总体而言，这些数据有力地支持了在人类中使用MVA85A作为增强剂，以扩大能够产生显著二次反应的多功能结核分枝杆菌特异性CD4(+)T细胞。
In the search for effective vaccines against intracellular pathogens such as HIV, tuberculosis and malaria, recombinant viral vectors are increasingly being used to boost previously primed T cell responses. Published data have shown prime-boost vaccination with BCG-MVA85A (modified vaccinia virus Ankara expressing antigen 85A) to be highly immunogenic in humans as measured by ex vivo IFN-gamma ELISPOT. Here, we used polychromatic flow cytometry to investigate the phenotypic and functional profile of these vaccine-induced Mycobacterium tuberculosis (M.tb) antigen 85A-specific responses in greater detail. Promisingly, antigen 85A-specific CD4(+) T cells were found to be highly polyfunctional, producing IFN-gamma, TNF-alpha, IL-2 and MIP-1 beta. Surface staining showed the responding CD4(+) T cells to be relatively immature (CD45RO(+) CD27(int)CD57(-)); this observation was supported by the robust proliferative responses observed following antigenic stimulation. Furthermore, these phenotypic and functional properties were independent of clonotypic composition and epitope specificity, which was maintained through the different phases of the vaccine-induced immune response. Overall, these data strongly support the use of MVA85A in humans as a boosting agent to expand polyfunctional M.tb-specific CD4(+) T cells capable of significant secondary responses.