首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Intradermal and oral immunization with recombinant Mycobacterium bovis BCG expressing the simian immunodeficiency virus Gag protein induces long-lasting, antigen-specific immune responses in guinea pigs.
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Intradermal and oral immunization with recombinant Mycobacterium bovis BCG expressing the simian immunodeficiency virus Gag protein induces long-lasting, antigen-specific immune responses in guinea pigs.

机译:表达猿猴免疫缺陷病毒Gag蛋白的重组牛分枝杆菌BCG的皮内和口服免疫在豚鼠中诱导持久的抗原特异性免疫反应。

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摘要

To develop a new recombinant BCG (rBCG) vaccine, we constructed rBCG that expresses the full-length Gag protein of simian immunodeficiency virus (rBCG-SIVGag) at a level of 0.5 ng/mg after 3 weeks of bacterial cell culture. Intradermal (i.d.) inoculation of guinea pigs with 0.1 mg of rBCG-SIVGag resulted in the induction of delayed-type hypersensitivity (DTH) responses to both purified protein derivative (PPD) of tuberculin and SIV Gag p27 protein; responses that were maintained for the duration of the 50-week study. In contrast, guinea pigs orally vaccinated with 160 mg of the same antigen exhibited a long-lasting DTH response to the SIV Gag p27 protein, but mounted no response to PPD. Proliferative responses to SIV Gag p27 and PPD antigens were detected in both i.d. and orally immunized animals; however, the levels of PPD-specific responses were significantly higher in guinea pigs immunized by the i.d. than the oral route. A significant increase in the level of PPD- and SIV Gag p27-specific IFNgamma mRNA expression was also detected in both immunization groups receiving rBCG-SIVGag. In addition, both i.d. and oral immunization with rBCG-SIVGag induced PPD- and SIV Gag p27-specific serum IgG responses. Insertion of the SIV gag gene into BCG did not appear to change the ability of rBCG-immunized animals to elicit PPD-specific immune responses. These results indicate that rBCG-SIVGag has the ability to effectively induce long-lasting, cell-mediated and humoral immunity against both viral and bacterial antigens in guinea pigs, suggesting that rBCG-Gag has the potential to elicit immunities specific not only for tuberculosis but also for HIV at human doses.
机译:为了开发新的重组BCG(rBCG)疫苗,我们构建了在细菌细胞培养3周后以0.5 ng / mg的水平表达猿猴免疫缺陷病毒(rBCG-SIVGag)全长Gag蛋白的rBCG。用0.1 mg rBCG-SIVGag皮内(i.d.)接种豚鼠导致诱导了对结核菌素的纯化蛋白衍生物(PPD)和SIV Gag p27蛋白的迟发型超敏反应(DTH);在为期50周的研究过程中保持的反应。相反,口服160 mg相同抗原的豚鼠对SIV Gag p27蛋白表现出持久的DTH反应,但对PPD没有反应。在两个体内均检测到对SIV Gag p27和PPD抗原的增殖反应。以及口服免疫的动物;但是,经i.d.免疫的豚鼠中PPD特异性反应的水平明显更高。比口服途径在接受rBCG-SIVGag的两个免疫组中,PPD和SIV Gag p27特异性IFNgamma mRNA表达水平也显着增加。此外,两者以及用rBCG-SIVGag口服免疫诱导的PPD和SIV Gag p27特异性血清IgG反应。 SIV gag基因插入BCG似乎没有改变rBCG免疫动物引发PPD特异性免疫反应的能力。这些结果表明,rBCG-SIVGag具有有效诱导豚鼠对病毒和细菌抗原的持久性,细胞介导的和体液免疫的能力,这表明rBCG-Gag有可能引发不仅针对结核病而且针对肺炎的特异性免疫。也适用于人类剂量的HIV。

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