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首页> 外文期刊>Vaccine >Cell-mediated immune responses to a varicella-zoster virus glycoprotein E vaccine using both a TLR agonist and QS21 in mice
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Cell-mediated immune responses to a varicella-zoster virus glycoprotein E vaccine using both a TLR agonist and QS21 in mice

机译：TLR激动剂和QS21在小鼠中对水痘带状疱疹病毒糖蛋白E疫苗的细胞介导的免疫反应

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摘要

Lack of adequate cell-mediated immunity (CMI) to varicella-zoster virus (VZV) has been associated with higher risks of developing herpes zoster (HZ) and associated post-herpetic neuralgia (PHN), and is of particular concern for older and immunocompromised individuals. Thus, the development of an effective HZ vaccine with a clinically acceptable safety profile that is capable of addressing decreased immunity would be highly desirable. In this study we compared the immunogenicity of different vaccine formulations containing VZV glycoprotein E (gE), an important target for CMI and antibody responses, in a VZV-primed mouse model. The formulations included recombinant gE, either unadjuvanted, or combined with aluminium salt or an Adjuvant System (AS01 or AS02), and CMI was used as the primary immunological endpoint. All adjuvanted vaccines induced gE- and/or VZV-specific CD4(+). T cell and antibody responses. A formulation of gE with an Adjuvant System containing the immunostimulants QS21 and 3-O-desacyl-4'-monophosphoryl lipid A (MPL) was shown to be more immunogenic than gE with aluminium salt or unadjuvanted gE (gE/saline). Both immunostimulants were shown to act synergistically in enhancing CMI responses. Formulations with AS01 elicited high frequencies of CD4(+). T cells producing IFN-gamma and IL-2. These responses were dose-dependent with respect to both antigen and adjuvant. The gE/AS01(B) candidate vaccine induced higher frequencies of CD4(+). T cells producing IL-2 and/or IFN-gamma than all other gE/AS01 formulations, supporting its use for clinical evaluations. (C) 2012 Elsevier Ltd. All rights reserved.
机译：对水痘带状疱疹病毒（VZV）缺乏足够的细胞介导的免疫（CMI）与发生带状疱疹（HZ）和相关的疱疹后神经痛（PHN）的风险较高相关，尤其是对于年龄较大且免疫功能低下的人个人。因此，非常需要开发一种具有临床可接受的安全性的有效HZ疫苗，其能够解决免疫力下降的问题。在这项研究中，我们比较了在VZV启动的小鼠模型中含有VZV糖蛋白E（gE）（CMI和抗体应答的重要靶标）的不同疫苗制剂的免疫原性。该制剂包括重组gE，可以是非佐剂的，也可以是与铝盐或佐剂系统（AS01或AS02）组合的，并且CMI被用作主要的免疫学终点。所有佐剂疫苗均可诱导gE和/或VZV特异性CD4（+）。 T细胞和抗体反应。具有佐剂系统的包含免疫刺激剂QS21和3-O-去酰基-4'-单磷酰基脂质A（MPL）的gE制剂比具有铝盐或未佐剂的gE（gE /盐水）的gE具有更高的免疫原性。两种免疫刺激剂均显示在增强CMI反应中起协同作用。含有AS01的配方引起高频率的CD4（+）。 T细胞产生IFN-γ和IL-2。这些反应对于抗原和佐剂都是剂量依赖性的。 gE / AS01（B）候选疫苗可诱导更高频率的CD4（+）。与所有其他gE / AS01制剂相比，产生IL-2和/或IFN-γ的T细胞，支持其用于临床评估。 （C）2012 Elsevier Ltd.保留所有权利。

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