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A vaccination strategy incorporating DNA priming and mucosal boosting using tetanus toxin fragment C (TetC)

机译：破伤风毒素片段C（TetC）结合了DNA引发和粘膜加强作用的疫苗接种策略

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Intramuscular (i.m.) immunisation of BALB/c mice with a DNA vaccine, pcDNA3/tetC. encoding fragment C (TetC) from tetanus toxin, stimulated production of TetC specific IgG2a antibodies in the serum and release of IFN-gamma from TetC stimulated splenocytes. A similar pattern of immune response was detected if pcDNA3/tetC primed mice were boosted i.m. with purified TetC protein or TetC and cholera toxin (included as an adjuvant). In contrast. control mice primed with the empty DNA vector pcDNA3 and boosted i.m. with TetC or TetC and CT. generated a dominant IgG1 specific anti-TetC response in the sera and low or undetectable levels of IFN-gamma from stimulated splenocytes. Thus, i.m. priming with a DNA vaccine modulated the subsequent immune response to the same antigen administered as a protein boost. Similar observations were made when DNA primed mice were boosted using the intranasal mucosal route of immunisation. Interestingly, although mice immunised with pcDNA3/tetC and boosted mucosally with TetC and CT produced anti-TetC IgA in mucosal secretions. the titres were reproducibly lower than those detected in mice immunised with the pcDNA3 vector alone. The immunomodulatory effect of pcDNA3/tetC appeared to be antigen specific as mucosal boosting with an unrelated antigen (pertactin) revealed no significant modulation in terms of the anti-pertactin immune response.
机译：用DNA疫苗pcDNA3 / tetC对BALB / c小鼠进行肌内（i.m.）免疫。破伤风毒素编码片段C（TetC），刺激TetC特异性IgG2a抗体在血清中产生以及从TetC刺激的脾细胞释放IFN-γ。如果pcDNA3 / tetC引发的小鼠在i.m免疫后被检测到类似的免疫反应模式。含有纯化的TetC蛋白或TetC和霍乱毒素（作为佐剂）。相反。对照小鼠用空的DNA载体pcDNA3灌注并增强免疫力。使用TetC或TetC和CT。在血清中产生了显性的IgG1特异性抗TetC反应，而受刺激的脾细胞中的IFN-γ水平低或不可检测。因此，我用DNA疫苗引发的启动子可调节随后对作为蛋白质加强剂施用的相同抗原的免疫反应。当使用鼻内粘膜免疫途径对DNA引发的小鼠进行加强免疫时，也得出了类似的观察结果。有趣的是，尽管用pcDNA3 / tetC免疫并用TetC和CT进行粘膜增强的小鼠在粘膜分泌物中产生了抗TetC IgA。滴度可重复地低于仅用pcDNA3载体免疫的小鼠中检测到的滴度。 pcDNA3 / tetC的免疫调节作用似乎是抗原特异性的，因为用不相关的抗原（pertactin）进行的粘膜强化显示出在抗pertactin免疫应答方面没有明显的调节作用。

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