免疫共刺激分子OX40L对乙型肝炎核酸疫苗的免疫佐剂作用

目的]为了进一步增强HBV DNA疫苗的免疫反应,本研究将共刺激分子OX40L 作为HBV DNA疫苗的分子佐剂免疫小鼠,旨在探讨共刺激分子OX40L对HBV DNA疫苗诱导体液和细胞免疫应答的影响.方法]我们将HBV DNA疫苗(pcDS2)单独或联合共刺激分子质粒pOX40L免疫C57BL/6小鼠;分别在第0,2,4周进行免疫,在第6周检测抗-HBs IgG、IgG1和IgG2a,T淋巴细胞增殖指数,细胞因子表达水平和体内细胞毒性T淋巴细胞杀伤作用(CTL)等免疫学指标.结果]pceDS2联合pOX40L免疫组小鼠的抗-HBs水平显著提高,抗-HBs IgG亚类以IgG2a占优;免疫小鼠的T淋巴细胞体外经乙型肝炎表面抗原(HBsAg)刺激后,联合免疫组刺激指数(SI)明显高于pcDS2组;联合免疫组CD4 + T淋巴细胞的IL-4和IFN-γ表达水平及CD8 + T淋巴细胞的IFN-γ表达水平显著升高;DNA疫苗免疫的各组小鼠,HBsAg特异性体内CTL高于对照组,其中联合免疫组小鼠的体内CTL杀伤作用最强.结论]共刺激分子OX40L不仅能增强HBV DNA疫苗诱导特异性体液免疫应答,还能增强特异性细胞免疫反应,尤其增强体内CTL的杀伤活性,为HBV DNA疫苗的研究奠定了基础.

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

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- in CD4+ T cell and IFN- 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- and IL-4 in CD4+ T cells and a higher level of IFN- 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.