Intracellular Targeting of CEA Results in Th1-Type Antibody Responses Following Intradermal Genetic Vaccination by a Needle-Free Jet Injection Device

Intracellular Targeting of CEA Results in Th1-Type Antibody Responses Following Intradermal Genetic Vaccination by a Needle-Free Jet Injection Device
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通过无针喷射注射装置进行皮内基因疫苗接种后,CEA 的细胞内靶向导致 Th1 型抗体反应

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发表时间:
2007
影响因子:
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通讯作者:
Kristian Hallermalm
Kristian Hallermalm
中科院分区:
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文献类型:
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作者:
S. Johansson;M. Ek;B. Wahren;R. Stout;Margaret A. Liu;Kristian Hallermalm

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免疫途径和方法,以及抗原的细胞定位,可以影响免疫反应的产生。一般来说,肌肉内免疫导致Th1应答,而通过基因枪免疫的DNA皮内递送通常导致更多的Th2应答。在这里,我们研究如何改变肿瘤抗原CEA(癌胚抗原)的细胞定位,影响DNA疫苗诱导的抗体反应的质量和振幅,随后通过无针喷射注射装置(Biojector)在小鼠皮内递送DNA。CEA要么以膜结合形式(野生型CEA)表达,要么以细胞质定位的两种截断形式(CEA6和CEA66)表达,其中CEA66与来自破伤风毒素的混杂t辅助表位融合。用编码野生型CEA的DNA反复皮内免疫BALB/c小鼠,产生IgG1/IgG2a混合比例的高抗体滴度。相反,利用导致细胞内靶向CEA的DNA结构导致诱导CEA特异性抗体的能力降低,但反而诱导了th1偏向性免疫反应。
The route and method of immunization, as well as the cellular localization of the antigen, can influence the generation of an immune response. In general, intramuscular immunization results in Th1 responses, whereas intradermal delivery of DNA by gene gun immunization often results in more Th2 responses. Here we investigate how altering the cellular localization of the tumor antigen CEA (carcinoembryonic antigen) affects the quality and amplitude of DNA vaccine-induced antibody responses in mice following intradermal delivery of DNA by a needle-free jet injection device (Biojector). CEA was expressed either in a membrane-bound form (wild-type CEA) or in two truncated forms (CEA6 and CEA66) with cytoplasmic localization, where CEA66 was fused to a promiscuous T-helper epitope from tetanus toxin. Repeated intradermal immunization of BALB/c mice with DNA encoding wild-type CEA produced high antibody titers of a mixed IgG1/IgG2a ratio. In contrast, utilizing the DNA construct that resulted in intracellular targeting of CEA led to a reduced capacity to induce CEA-specific antibodies, but instead induced a Th1-biased immune response.
编码具有快速蛋白酶体依赖性降解的抗原的脱氧核糖核酸疫苗是溶细胞性 T 淋巴细胞的高效诱导剂。
DOI: --
发表时间: 1997
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Wu,Y;Kipps,TJ
通讯作者: Kipps,TJ
磷脂酰肌醇特异性磷脂酶 C 从人结肠癌细胞中释放癌胚抗原。
DOI: 10.1172/jci113636
发表时间: 1988
期刊: The Journal of clinical investigation
影响因子: --
作者:
Sack,TL;Gum,JR;Low,MG;Kim,YS
通讯作者: Kim,YS