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针对产肠毒素大肠杆菌的新型疫苗策略。I:针对CFA/I菌毛黏附素的DNA疫苗。

New vaccine strategies against enterotoxigenic Escherichia coli. I: DNA vaccines against the CFA/I fimbrial adhesin.

作者信息

Alves A M, Lásaro M O, Almeida D F, Ferreira L C

机构信息

Laboratorio de Fisiologia Celular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brasil.

出版信息

Braz J Med Biol Res. 1999 Feb;32(2):223-9. doi: 10.1590/s0100-879x1999000200011.

Abstract

Stimulation of the mammalian immune system by administration of plasmid DNA has been shown to be an important approach for vaccine development against several pathogens. In the present study we investigated the use of DNA vaccines to induce immune responses against an enteric bacterial pathogen, enterotoxigenic Escherichia coli (ETEC). Three plasmid vectors encoding colonization factor antigen 1 (CFA/I), an ETEC fimbrial adhesin, were constructed. Eukaryotic cells transfected with each of these plasmids expressed the heterologous antigen in different compartments: bound to the cytoplasmic membrane (pRECFA), accumulated in the cytoplasm (pPolyCFA) or secreted to the outside medium (pBLCFA). BALB/c mice were intramuscularly (i.m.) inoculated with purified plasmid DNA and the systemic, cellular and secreted CFA/I-specific immune responses were analyzed. The results showed that all three DNA vaccine formulations could elicit CFA/I-specific immune responses. Moreover, cellular location of the plasmid-encoded CFA/I seems to have an important role in the induced immune response. Taken together, these results indicate that DNA vaccines also represent a promising approach against enteric bacterial pathogens.

摘要

通过给予质粒DNA刺激哺乳动物免疫系统已被证明是开发针对多种病原体疫苗的重要方法。在本研究中,我们研究了使用DNA疫苗诱导针对肠道细菌病原体产肠毒素大肠杆菌(ETEC)的免疫反应。构建了三种编码定居因子抗原1(CFA/I)(一种ETEC菌毛粘附素)的质粒载体。用这些质粒中的每一种转染的真核细胞在不同区室中表达异源抗原:与细胞质膜结合(pRECFA)、在细胞质中积累(pPolyCFA)或分泌到外部培养基中(pBLCFA)。将BALB/c小鼠肌肉注射纯化的质粒DNA,并分析全身、细胞和分泌的CFA/I特异性免疫反应。结果表明,所有三种DNA疫苗制剂均可引发CFA/I特异性免疫反应。此外,质粒编码的CFA/I的细胞定位似乎在诱导的免疫反应中起重要作用。综上所述,这些结果表明DNA疫苗也是对抗肠道细菌病原体的一种有前景的方法。

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