Improving recombinant MVA immune responses:: Potentiation of the immune responses to HIV-1 with MVA and DNA vectors expressing Env and the cytokines IL-12 and IFN-gamma
Improving recombinant MVA immune responses:: Potentiation of the immune responses to HIV-1 with MVA and DNA vectors expressing Env and the cytokines IL-12 and IFN-gamma
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DOI：
10.1016/j.virusres.2005.08.008
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发表时间：
2006-03-01
期刊：
影响因子：
5
通讯作者：
Esteban, M
中科院分区：
文献类型：
--
作者：
Abaitua, F;Rodríguez, JR;Esteban, M
基于稀释剂的油牛痘病毒载体，特别是高度减毒的修饰牛痘病毒安卡拉（MVA）株，正在临床试验中使用初免/加强异源接种方案进行安全性和免疫原性的流动测试。由于MVA的复制能力有限，有必要开发可以增强对MVA载体递送的重组抗原的特异性细胞免疫应答的方法。在这项研究中，我们表征了以佐剂样方式使用干扰素-γ（IFN-gamma）或白细胞介素-12（IL-12）在BALB/c小鼠中的全身免疫反应，这些免疫反应是由表达这些细胞因子之一的MVA重组体或裸DNA载体与人类免疫缺陷病毒I型（HIV-1）包膜（Env）作为抗原引起的。在感染的小鼠中，脾细胞中的病毒基因表达和血清中细胞因子IFN-γ和IL-12的水平在用表达IFN-γ（MVAIFN-γ）或IL-12（MVAIL-12）的MVA重组体感染后（hpi）61 f达到最大。在感染的动物中，HIV-1 env（MVAENV）和来自MVA重组体的IFN-γ或IL-12的共表达分别使抗env CD 8 + T细胞应答增加2倍和3倍。当用表达HIV-1 env和IFN-γ或IL-12的DNA载体进行初免时，MVAENV加强后特异性抗env CD 8 + T细胞刺激的幅度进一步增强。我们的研究结果表明，IFN-γ或IL-12可用于增强对HIV-1 env的细胞免疫应答，无论是从单个MVA重组体还是从DNA载体递送。在DNA/MVA初免/加强方案中，CD 8 + T细胞应答的增量更高。因此，MVA载体的免疫应答可以通过细胞因子IFN-γ或IL-12的共递送来改善。(c)2005 Elsevier B. V.保留所有权利。
Recombinants based oil vaccinia Virus vectors, especially oil the highly attenuated modified vaccinia Virus Ankara (MVA) strain, are flow being tested in clinical trials for safety and immunogenicity, using prime/boost heterologous regimes of vaccination. Due to file limited replication capacity of MVA, it is necessary to develop procedures that can enhance the specific cellular immune responses to the recombinant antigen delivered by the MVA vector. In this investigation, we have characterized the systemic immune responses in BALB/c Mice using interferon-gamma (IFN-gamma) or interleukin-12 (IL-12) in an adjuvant-like manner elicited by MVA recombinants or naked DNA vectors expressing one of those cytokines in combination with the human immunodeficiency virus type I (HIV-1) envelope (Env) as antigen. In infected mice, virus gene expression in splenocytes and levels of cytokines IFN-gamma and IL-12 in serum were maximal by 6 If post-infection (hpi) with MVA recombinants expressing IFN-gamma (MVAIFN-gamma)or IL-12 (MVAIL-12). In the infected animals,co-expression of HIV-1 env (MVAENV) and either IFN-gamma or IL-12 from MVA recombinants produced a two and three-fold increase of anti-env CD8+ T cell response, respectively. When priming was carried Out with DNA vectors expressing HIV-1 env and either IFN-gamma or IL-12, the magnitude of the specific anti-env CD8+ T cell stimulation after MVAENV booster Was further enhanced. Our findings revealed that IFN-gamma or IL-12 can be used to potentiate the cellular immune response to HIV-1 env, when delivered either from a single MVA recombinant or from a DNA vector. The increment of the CD8+ T cell response was higher in a DNA/MVA prime/boost protocol. Thus, the immune response of MVA vectors can be improved with the co-delivery of the cytokines IFN-gamma or IL-12. (c) 2005 Elsevier B.V. All rights reserved.