Wen Jiejun, Hao Wenli, Fan Yan, Du Jiani, Du Bing, Qian Min, Jiang Wenzheng
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.
Arch Virol. 2014 Jul;159(7):1663-9. doi: 10.1007/s00705-014-1981-y. Epub 2014 Jan 17.
The immunogenicity and efficacy of a DNA vaccine can be greatly enhanced when a gene adjuvant is used. LIGHT, a member of TNF superfamily, can function as a costimulatory molecule for human naïve T cells to proliferate and can be a potential gene adjuvant. In the current study, the eukaryotic expression plasmid pcDNA-nef was constructed by inserting a full-length nef gene into pcDNA3.1(+), and an in vitro transfection experiment suggested that the nef gene could be expressed successfully in mammalian cells. BALB/c mice were immunized with HIV-1 nef DNA vaccine plasmids alone or in combination with LIGHT expression plasmids, and the specific humoral and cellular immune responses were measured. The data showed that HIV-1 nef DNA vaccine plasmids could induce anti-Nef antibodies, Nef-specific lymphocyte proliferation and CTL activity, whereas stronger specific immune responses were induced in mice when co-immunizing with HIV-1 nef DNA vaccine plasmids and LIGHT expression plasmids, suggesting that the eukaryotic expression vector encoding HIV-1 nef is capable of inducing specific immune responses towards HIV-1 Nef and that LIGHT could be considered as a gene adjuvant for HIV-1 DNA vaccination.
当使用基因佐剂时，DNA疫苗的免疫原性和效力可得到极大增强。LIGHT是肿瘤坏死因子超家族的成员之一，可作为人初始T细胞增殖的共刺激分子，并且可能是一种潜在的基因佐剂。在本研究中，通过将全长nef基因插入pcDNA3.1(+)构建真核表达质粒pcDNA-nef，体外转染实验表明nef基因可在哺乳动物细胞中成功表达。用HIV-1 nef DNA疫苗质粒单独或与LIGHT表达质粒联合免疫BALB/c小鼠，并检测特异性体液免疫和细胞免疫反应。数据显示，HIV-1 nef DNA疫苗质粒可诱导抗Nef抗体、Nef特异性淋巴细胞增殖和CTL活性，而当与HIV-1 nef DNA疫苗质粒和LIGHT表达质粒共同免疫时，小鼠体内诱导出更强的特异性免疫反应，这表明编码HIV-1 nef的真核表达载体能够诱导针对HIV-1 Nef的特异性免疫反应，并且LIGHT可被视为HIV-1 DNA疫苗接种的基因佐剂。
