Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, China.
School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China.
Front Immunol. 2018 Aug 3;9:1796. doi: 10.3389/fimmu.2018.01796. eCollection 2018.
The kinds of vaccine-induced T cell responses that are beneficial for protection against () infection are not adequately defined. We had shown that a novel Sendai virus vectored vaccine, SeV85AB, was able to enhance immune protection induced by bacille Calmette-Guérin (BCG) in a prime-boost model. However, the profile of T cell responses boosted by SeV85AB was not determined. Herein, we show that the antigen-specific CD4 and CD8 T cell responses were both enhanced by the SeV85AB boost after BCG. Different profiles of antigen-specific po T cell subsets were induced in the local (lung) and systemic (spleen) sites. In the spleen, the CD4 T cell responses that were enhanced by the SeV85AB boost were predominately IL-2 responses, whereas in the lung the greater increases were in IFN-γ- and TNF-α-producing CD4 T cells; in CD8 T cells, although IFN-γ was enhanced in both the spleen and lung, only IL-2TNF-αCD8 T subset was boosted in the latter. After a challenge infection, there were significantly higher levels of recall IL-2 responses in T cells. In contrast, IFN-γ-producing cells were barely boosted by SeV85AB. After challenge a central memory phenotype of responding CD4 T cells was a prominent feature in SeV85AB-boosted mice. Thus, our data strongly suggest that the enhanced immune protection induced by SeV85AB boosting was associated with establishment of an increased capacity to recall antigen-specific IL-2-mediated T cell responses and confirms this Sendai virus vector system as a promising candidate to be used in a heterologous prime-boost immunization regimen against TB.
针对()感染,能产生有益保护作用的疫苗诱导 T 细胞反应类型尚未充分明确。我们曾表明,新型仙台病毒载体疫苗 SeV85AB 能够增强卡介苗(BCG)在初次-加强免疫模型中的免疫保护作用。然而,尚未明确 SeV85AB 增强的 T 细胞反应特征。在此,我们显示 BCG 后,SeV85AB 加强可增强抗原特异性 CD4 和 CD8 T 细胞反应。在局部(肺)和全身(脾)部位诱导了不同的抗原特异性初始 T 细胞亚群。在脾,SeV85AB 加强增强的 CD4 T 细胞反应主要为 IL-2 反应,而在肺,IFN-γ和 TNF-α产生的 CD4 T 细胞增加更多;在 CD8 T 细胞中,虽然 IFN-γ在脾和肺中均增强,但仅在后者中增强了 IL-2TNF-αCD8 T 亚群。感染后,T 细胞中可回忆的 IL-2 反应水平显著升高。相比之下,IFN-γ产生细胞很少被 SeV85AB 增强。感染后,在 SeV85AB 增强的小鼠中,应答 CD4 T 细胞的中央记忆表型是一个显著特征。因此,我们的数据强烈表明,SeV85AB 增强免疫保护作用与增强抗原特异性 IL-2 介导的 T 细胞反应的能力有关,并证实该仙台病毒载体系统是针对结核分枝杆菌的异源初次-加强免疫方案的有前途的候选者。