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菜籽油籽和大肠杆菌衍生的丙型肝炎病毒 (HCV) 核心蛋白与油体佐剂一起,在免疫接种的小鼠中诱导出强烈的 Th1 定向免疫反应。

Canola oilseed- and Escherichia coli- derived hepatitis C virus (HCV) core proteins adjuvanted with oil bodies, induced robust Th1-oriented immune responses in immunized mice.

机构信息

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran.

出版信息

APMIS. 2020 Nov;128(11):593-602. doi: 10.1111/apm.13074. Epub 2020 Sep 21.

Abstract

Induction of broad Th1 cellular immune responses and cytokines is crucial characteristics for vaccines against intracellular infections such as hepatitis C virus (HCV). Plants (especially oilseed tissues) and plant-immunomodulators (like oil bodies) offer cost-effective and scalable possibilities for the production of immunologically relevant and safe vaccine antigens and adjuvants, respectively. Herein, we provide data of the murine immunization by transgenic canola oilseed-derived HCV core protein (HCVcp) soluble extract (TSE) and Escherichia coli- derived rHCVcp in combination with Canola oil bodies (oil) compared to that of the Freund's (FA) adjuvant. Mice immunized by TSE+ oil developed both strong humeral (IgG) and Th1-biased cellular responses, manifested by high levels of IFN-γ and lower IgG1/IgG2a ratio and IL-4 secretion. Results of the intracellular cytokine staining indicated that TSE+ oil immunization in mice triggered both CD4 and CD8 T cells to release IFN-γ, while CD4 cells were mostly triggered when FA was used. Analyses by qRT-PCR indicated that a combination of rHCVcp/TSE with oil body induced high levels of IL-10 cytokines compared to that of the FA adjuvant. These characteristics are important properties for the design of an HCV vaccine candidate and indicate the potential of Canola-derived antigen and oil bodies in addressing these concerns.

摘要

诱导广泛的 Th1 细胞免疫反应和细胞因子是针对细胞内感染(如丙型肝炎病毒 (HCV))疫苗的关键特征。植物(特别是油籽组织)和植物免疫调节剂(如油体)为生产具有免疫相关性和安全性的疫苗抗原和佐剂分别提供了具有成本效益和可扩展性的可能性。在此,我们提供了转基因油菜籽油体衍生 HCV 核心蛋白 (HCVcp) 可溶性提取物 (TSE) 和大肠杆菌衍生 rHCVcp 与油菜籽油体 (油) 联合免疫小鼠的数据,与 Freund 佐剂 (FA) 进行比较。用 TSE+油免疫的小鼠产生了强烈的体液(IgG)和 Th1 偏向的细胞反应,表现为高水平的 IFN-γ和较低的 IgG1/IgG2a 比值和 IL-4 分泌。细胞内细胞因子染色的结果表明,TSE+油免疫可诱导 CD4 和 CD8 T 细胞释放 IFN-γ,而当使用 FA 时,主要诱导 CD4 细胞。qRT-PCR 分析表明,与 FA 佐剂相比,rHCVcp/TSE 与油体的组合诱导了高水平的 IL-10 细胞因子。这些特性是 HCV 疫苗候选物设计的重要特性,并表明油菜衍生抗原和油体在解决这些问题方面的潜力。

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