Department of Immunology, China Medical University, 92, North Second Road, Heping District, Shenyang 110001, China.
Vaccine. 2010 Apr 19;28(18):3134-42. doi: 10.1016/j.vaccine.2010.02.058. Epub 2010 Mar 1.
Tuberculosis is one of the leading causes of mortality from an infectious disease worldwide, however, the efficacy of BCG vaccine against adult pulmonary tuberculosis still remains instability. Therefore, it is an urgent work to develop both safe and effective vaccine to TB. To clarify the liposome encapsulated DNA vaccine was effectively working as a vaccine delivery system to evoke mucosal intestinal immune responses. A Mycobacterium pcDNA3.1(+)/Ag85A DNA was constructed and encapsulated into liposome. Ag85A protein antigen was observed to substantially express in the epithelium, microfold cells (M cells), dendritic cells (DCs) and Peyer's patches (pp) of the small intestine, respectively, after oral administration into C57BL/6 mice 3 times each 14 days interval. Furthermore, levels of IL-2 and IFN-gamma in the IELs isolated from the small intestine were markedly increased, IL-4 level was not significantly changed as compared to those in control group after oral administration of Ag85A DNA encapsulated in liposome, together with the augmented Ag85A-specific cytotoxicity of IELs, indicating a local Th1 dominant cellular immune response was elicited, and thus enhanced cytotoxicity of IELs as compared to those in control mice. Furthermore, sIgA level was also elevated in liposomal encapsulated Ag85A DNA immunized mice. These data indicated that oral vaccination with the liposomal-pcDNA 3.1(+)/Ag85A DNA is able to induce antigen specific mucosal cellular and humoral immune responses. Especially, cellular compartment in the epithelium of small intestine plays a key role on the regulation of immune response to eliminate TB. These findings have important understanding and possible implications for the design of new strategies based on oral DNA vaccine on regulation of immune response in protection against TB. Further study is clearly necessary to improve the effectiveness of Ag85A DNA vaccines against TB as compared with BCG.
结核病是全球传染病导致死亡的主要原因之一,然而,卡介苗(BCG)疫苗对成人肺结核的疗效仍然不稳定。因此,开发安全有效的结核病疫苗是当务之急。为了阐明脂质体包封的 DNA 疫苗作为疫苗传递系统有效地引发粘膜肠道免疫反应。构建并包封了 Mycobacterium pcDNA3.1(+)/Ag85A DNA 进入脂质体。在给 C57BL/6 小鼠口服 Ag85A DNA 脂质体 3 次,每次间隔 14 天,分别观察到 Ag85A 蛋白抗原在小肠的上皮细胞、微褶皱细胞(M 细胞)、树突状细胞(DC)和派尔集合淋巴结(pp)中大量表达。此外,与对照组相比,口服脂质体包封的 Ag85A DNA 后,从小肠分离的 IELs 中 IL-2 和 IFN-γ水平显著升高,IL-4 水平无明显变化,同时 IELs 的 Ag85A 特异性细胞毒性增强,表明诱导了局部 Th1 优势细胞免疫反应,并因此增强了 IELs 的细胞毒性与对照组相比。此外,脂质体包封的 Ag85A DNA 免疫小鼠的 sIgA 水平也升高。这些数据表明,用脂质体-pcDNA3.1(+)/Ag85A DNA 口服免疫能够诱导抗原特异性粘膜细胞和体液免疫反应。特别是,小肠上皮细胞中的细胞区室在调节免疫反应以消除结核病方面发挥着关键作用。这些发现对于基于口服 DNA 疫苗设计新的免疫反应调节策略以预防结核病具有重要的理解和可能的意义。显然需要进一步研究,以提高 Ag85A DNA 疫苗对结核病的有效性,与 BCG 相比。