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首页> 外文期刊>Vaccine >A combined DNA vaccine enhances protective immunity against Mycobacterium tuberculosis and Brucella abortus in the presence of an IL-12 expression vector
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A combined DNA vaccine enhances protective immunity against Mycobacterium tuberculosis and Brucella abortus in the presence of an IL-12 expression vector

机译:在存在IL-12表达载体的情况下,联合使用的DNA疫苗增强了针对结核分枝杆菌和流产布鲁氏菌的保护性免疫

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We examined the immunogenicity and protective efficacy of a combined DNA vaccine that included six genes encoding immunodominant antigens from Mycobacterium tuberculosis and Brucella abortus. The IL-12 adjuvant system was used for immunization in combination with the combined DNA vaccine (DNA-IL-12(+)). Mice immunized with DNA-IL-12(+) had significantly reduced CFU counts for M. tuberculosis and B. abortus in lung and spleen, respectively (P<0.001), and DNA-IL-12(+) elicited better protection than the combined DNA vaccine alone (DNA-IL-12(-)) or with the positive control groups after challenge with a virulent M. tuberculosis strain and B. abortus 2308 infection. The DNA-IL-12(+) group had stronger antigen-specific IFN-gamma ELISPOT activities and higher levels of antigen-specific CD4(+) and CD8(+) T cell responses than either the DNA-IL-12(-) or positive control groups. Likewise, antigen-specific IgG titers were also much higher than in other immunized groups. Moreover, DNA-IL-12(+) gave a stronger IgG2a-skewed response than did DNA-IL-12(-). In addition, its mean concentrations of IFN-gamma and IL-2 were about 2.5- to 4.5-fold higher than those observed in the DNA-IL-12(-)-treated mice, and were significantly higher than control groups (P<0.01 or P<0.001), whereas IL-4 and IL-10 secretion were lower. These results suggest that IL-12 acts as an adjuvant to enhance protective immunity against M. tuberculosis and B. abortus through the induction of stronger Th1-associated immune responses. This is the first report to show that a single combined DNA vaccine protects animals against two infectious diseases.
机译:我们检查了组合DNA疫苗的免疫原性和保护功效,该疫苗包括六个编码结核分枝杆菌和流产布鲁氏菌免疫优势抗原的基因。 IL-12佐剂系统与联合DNA疫苗(DNA-IL-12(+))结合用于免疫。用DNA-IL-12(+)免疫的小鼠肺结核和脾脏中结核分枝杆菌和流产双歧杆菌的CFU计数分别显着降低(P <0.001),而DNA-IL-12(+)引起的保护作用优于对小鼠的保护。在使用强毒结核分枝杆菌菌株和流产双歧杆菌2308感染后,可单独使用DNA疫苗(DNA-IL-12(-))或与阳性对照组混合使用。与DNA-IL-12(-)相比,DNA-IL-12(+)组具有更强的抗原特异性IFN-γELISPOT活性和更高水平的抗原特异性CD4(+)和CD8(+)T细胞应答。或阳性对照组。同样,抗原特异性IgG滴度也比其他免疫组高得多。此外,DNA-IL-12(+)比DNA-IL-12(-)产生更强的IgG2a偏斜反应。此外,其IFN-γ和IL-2的平均浓度比在DNA-IL-12(-)处理的小鼠中观察到的平均浓度高约2.5-4.5倍,并且显着高于对照组(P < 0.01或P <0.001),而IL-4和IL-10分泌较低。这些结果表明,IL-12通过诱导更强的Th1相关的免疫应答,作为佐剂来增强针对结核分枝杆菌和流产芽孢杆菌的保护性免疫。这是第一份表明单一联合DNA疫苗可保护动物免受两种传染病侵害的报告。

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