Efficient vaccination by intradermal or intramuscular inoculation of plasmid DNA expressing hepatitis B surface antigen under desmin promoter/enhancer control.

Efficient vaccination by intradermal or intramuscular inoculation of plasmid DNA expressing hepatitis B surface antigen under desmin promoter/enhancer control.
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通过皮内或肌肉内接种在结蛋白启动子/增强子控制下表达乙型肝炎表面抗原的质粒 DNA 进行有效疫苗接种。

DOI:
10.1016/s0264-410x(00)00030-x
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发表时间:
2000
期刊:
影响因子:
5.5
通讯作者:
R. Schirmbeck
R. Schirmbeck
中科院分区:
医学3区
文献类型:
--
作者:
M. Kwissa;V. K. von Kampen;R. Zurbriggen;R. Glück;J. Reimann;R. Schirmbeck

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将乙型肝炎病毒的小表面抗原 (HBsAg) 克隆到病毒 (CMV) 启动子/增强子序列控制(质粒 pCI/S)或人结蛋白启动子/增强子序列控制(质粒 pDes/S)下的表达质粒 pCI 中。不同物种和组织来源的细胞在体外用 pCI/S 或 pDes/S 质粒 DNA 瞬时转染,表达可容易检测到的 HBsAg 量,无论是在细胞内(从细胞裂解物中沉淀),还是作为分泌产物(在 ELISA 中可检测到)。当这些质粒用于 DNA 疫苗接种时,在 Balb/c 小鼠中单次注射后,均能有效引发针对 HBsAg 的体液和/或细胞免疫反应。肌内注射两种质粒的高剂量 DNA(100 μg/小鼠)可在所有接种疫苗的小鼠中引发同等程度的 MHC-I 限制性细胞毒性 T 淋巴细胞 (CTL) 反应和 Th1 血清抗体反应(IgG1/IgG2a 比率 0.4–0.7)。使用基因枪皮内注射两种质粒的低剂量(颗粒包被的)DNA(1 μg/小鼠)引发 Th2 血清抗体反应(IgG1/IgG2a 比率 >100),但没有 CTL 反应。数据表明,抗原可以在病毒或真核启动子/增强子控制下有效表达,以实现体内免疫原性呈现,但DNA注射的技术、剂量和/或途径在确定引发的免疫反应类型方面具有决定性作用。
The small surface antigen of the hepatitis B virus (HBsAg) was cloned into expression plasmid pCI under either a viral (CMV) promoter/enhancer sequence control (plasmid pCI/S), or a human desmin promoter/enhancer sequence control (plasmid pDes/S). Cells of different species and tissue origin transiently transfected in vitro with pCI/S or pDes/S plasmid DNA expressed readily detectable amounts of HBsAg, either intracellularly (precipitated from cell lysates), or as secreted products (detectable in ELISA). When these plasmids were used in DNA vaccination, both efficiently primed humoral and/or cellular immune responses to HBsAg after a single injection in Balb/c mice. Intramuscular injection of a high dose of DNA (100 μg/mouse) of both plasmids primed MHC-I-restricted cytotoxic T lymphocyte (CTL) responses and Th1 serum antibody responses (IgG1/IgG2a ratio 0.4–0.7) of comparable magnitude in all vaccinated mice. Intradermal injection of low doses of (particle-coated) DNA (1 μg/mouse) of both plasmids with the gene gun primed Th2 serum antibody responses (IgG1/IgG2a ratio >100) but no CTL responses. The data indicate that antigens can be efficiently expressed under viral or eukaryotic promoter/enhancer control for immunogenic in vivo presentation, but that the technique, dose and/or route of DNA injection have a decisive role in determining the type of immune response elicited.
基因枪和肌内 DNA 免疫对靶位点组织的不同依赖性。
DOI: --
发表时间: 1997
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Torres,CA;Iwasaki,A;Barber,BH;Robinson,HL
通讯作者: Robinson,HL