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[质粒载体表达的OX40L对B型肝炎候选DNA疫苗的佐剂效应]

[Adjuvant effect of plasmid vector-expressed OX40L on candidate DNA vaccine against type B heptatitis].

作者信息

Du Xiaogang, Kang Youming, Wang Xiao, Wang Junpeng, Zhao Gan, Wang Bin

机构信息

Appled Biophysics and Immune Engineering Laboratory, College of Life and Physical Science, Sichuan Agricultural University, Ya'an 625014, China.

出版信息

Wei Sheng Wu Xue Bao. 2009 Mar;49(3):357-62.

PMID:19623960
Abstract

OBJECTIVE

To improve the immune response to HBsAg DNA vaccine and clear HBV, we investigated co-stimulatory molecule OX40L as adjuvant effect on the humoral and cellular immune responses to HBV DNA vaccine by immunizing mice with HBV DNA vaccine plus OX40L.

METHODS

We immunized the C57BL/6 mice with pcDS2 alone, or with OX40L and candidate DNA vaccine against HBV (pcDS2) together by intramuscular injection. The immunization was performed on week 0, 2, 4. The concentration of the anti-HBs (IgG) and isotypes (IgG1, IgG2a), the stimulated index of T lymphocyte proliferation, and the expression of IL-4 and IFN-gamma in CD4+ T cell and IFN-gamma in CD8+ T cell, specific in vivo cytotoxic T lymphocyte (CTL) activity were detected at week 6.

RESULTS

The concentration of the anti-HBs IgG induced by pcDS2 plus OX40L groups was much higher than that induce by pcDS2 alone, and the levels of IgG isotype of IgG2a were generally higher than IgG1 in all groups of mice immunized with different plasmids. Compared to mice immunized with pcDS2 alone, the pcDS2 plus OX40L group increased the stimulated index (SI) of T cell proliferation and elicited a higher level of IFN-gamma and IL-4 in CD4+ T cells and a higher level of IFN-gamma in CD8+ T cells. In all groups, OX40L plus pcDS2 induced significantly robust in vivo CTL response.

CONCLUSION

The co-immunization of OX40L and HBV DNA vaccine can enhance the humoral and cellular immune responses, especially CTL activity.

摘要

目的

为提高对乙肝表面抗原(HBsAg)DNA疫苗的免疫应答并清除乙肝病毒(HBV),我们通过用HBV DNA疫苗加OX40L免疫小鼠,研究共刺激分子OX40L作为佐剂对HBV DNA疫苗体液免疫和细胞免疫应答的影响。

方法

我们通过肌肉注射,单独用pcDS2或同时用OX40L和候选HBV DNA疫苗(pcDS2)免疫C57BL/6小鼠。在第0、2、4周进行免疫。在第6周检测抗-HBs(IgG)及其亚型(IgG1、IgG2a)的浓度、T淋巴细胞增殖刺激指数、CD4+ T细胞中IL-4和IFN-γ的表达以及CD8+ T细胞中IFN-γ的表达、体内特异性细胞毒性T淋巴细胞(CTL)活性。

结果

pcDS2加OX40L组诱导产生的抗-HBs IgG浓度远高于单独用pcDS2诱导产生的浓度,在用不同质粒免疫的所有小鼠组中,IgG2a亚型的水平普遍高于IgG1。与单独用pcDS2免疫的小鼠相比,pcDS2加OX40L组提高了T细胞增殖刺激指数(SI),并在CD4+ T细胞中引发了更高水平的IFN-γ和IL-4,在CD8+ T细胞中引发了更高水平的IFN-γ。在所有组中,OX40L加pcDS2诱导了显著更强的体内CTL应答。

结论

OX40L与HBV DNA疫苗联合免疫可增强体液免疫和细胞免疫应答,尤其是CTL活性。

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