Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, PR China.
Vaccine. 2012 Jul 6;30(32):4719-27. doi: 10.1016/j.vaccine.2012.05.040. Epub 2012 May 28.
We showed previously that calcineurin B subunit (CnB) protein activates innate immune cells including macrophages, monocytes and dendritic cells and acts as an adjuvant of a model antigen (ovalbumin) and a recombinant pneumolysin antigen, but the detailed mechanism is not clear and whether it can serve as an adjuvant of a commercial HBV vaccine is unknown. Here, we report that CnB promotes inflammatory cytokines production, splenocytes proliferation and NK lytic activity, and that CnB-induced inflammatory cytokines (IFN-γ, IL-6, TNF-α) production is dependent on integrin αM. Animal experiments demonstrate that CnB markedly increases the total anti-HBs antibodies in a dose and time dependent manner. Furthermore, CnB increases both anti-HBs IgM and anti-HBs IgG titers and changes the balance of IgG2a and IgG1. Combined use of CnB and CpG induces more cytokines production in splenocytes, as well as more anti-HBs antibodies production in vivo. These results reveal a probable mechanism of CnB-induced inflammatory cytokines production and further demonstrate that CnB is a novel and effective adjuvant of Engerix-B HBV vaccine.
我们之前已经证明钙调神经磷酸酶 B 亚基（CnB）蛋白可以激活固有免疫细胞，包括巨噬细胞、单核细胞和树突状细胞，并作为模型抗原（卵清蛋白）和重组肺炎球菌溶血素抗原的佐剂发挥作用，但详细机制尚不清楚，也不知道它是否可以作为乙肝疫苗（Engerix-B）的佐剂。在这里，我们报告 CnB 可促进炎性细胞因子的产生、脾细胞的增殖和 NK 溶细胞活性，并且 CnB 诱导的炎性细胞因子（IFN-γ、IL-6、TNF-α）的产生依赖于整合素 αM。动物实验表明，CnB 以剂量和时间依赖的方式显著增加总抗-HBs 抗体。此外，CnB 增加了抗-HBs IgM 和抗-HBs IgG 滴度，并改变了 IgG2a 和 IgG1 的平衡。CnB 与 CpG 的联合使用可在体内诱导更多的细胞因子产生，以及更多的抗-HBs 抗体产生。这些结果揭示了 CnB 诱导炎性细胞因子产生的可能机制，并进一步证明 CnB 是乙肝疫苗（Engerix-B）的一种新型有效佐剂。
