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首页> 美国卫生研究院文献>Journal of Virology >Improvement of hepatitis B virus DNA vaccines by plasmids coexpressing hepatitis B surface antigen and interleukin-2.
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Improvement of hepatitis B virus DNA vaccines by plasmids coexpressing hepatitis B surface antigen and interleukin-2.

机译：通过共表达乙型肝炎表面抗原和白介素2的质粒改进乙型肝炎病毒DNA疫苗。

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DNA vaccines encoding a viral protein have been shown to induce antiviral immune responses and provide protection against subsequent viral challenge. In this study, we show that the efficacy of a DNA vaccine can be greatly improved by simultaneous expression of interleukin-2 (IL-2). Plasmid vectors encoding the major (S) or middle (pre-S2 plus S) envelope proteins of hepatitis B virus (HBV) were constructed and compared for their potential to induce hepatitis B surface antigen (HBsAg)-specific immune responses with a vector encoding the middle envelope and IL-2 fusion protein or with a bicistronic vector separately encoding the middle envelope protein and IL-2. Following transfection of cells in culture with these HBV plasmid vectors, we found that the encoded major protein was secreted while the middle protein and the fusion protein were retained on the cell membrane. Despite differences in localization of the encoded antigens, plasmids encoding the major or middle proteins gave similar antibody and T-cell proliferative responses in the vaccinated animals. The use of plasmids coexpressing IL-2 and the envelope protein in the fusion or nonfusion context resulted in enhanced humoral and cellular immune responses. In addition, the vaccine efficacy in terms of dosage used in immunization was increased at least 100-fold by coexpression of IL-2. We also found that DNA vaccines coexpressing IL-2 help overcome major histocompatibility complex-linked nonresponsiveness to HBsAg vaccination. The immune responses elicited by HBV DNA vaccines were also modulated by coexpression of IL-2. When restimulated with antigen in vitro, splenocytes from mice that received plasmids coexpressing IL-2 and the envelope protein produced much stronger T helper 1 (Th1)-like responses than did those from mice that had been given injections of plasmids encoding the envelope protein alone. Coexpression of IL-2 also increased the Th2-like responses, although the increment was much less significant.
机译：已显示出编码病毒蛋白的DNA疫苗可诱导抗病毒免疫反应并提供针对后续病毒攻击的保护作用。在这项研究中，我们表明可以通过同时表达白介素2（IL-2）大大提高DNA疫苗的功效。构建了编码乙型肝炎病毒（HBV）主要（S）或中型（S2前加S）前包膜蛋白的质粒载体，并与编码BV的载体比较了它们诱导乙型肝炎表面抗原（HBsAg）特异性免疫应答的潜力中间包膜和IL-2融合蛋白，或带有双顺反子载体，分别编码中间包膜蛋白和IL-2。用这些HBV质粒载体转染培养的细胞后，我们发现编码的主要蛋白被分泌，而中间蛋白和融合蛋白则保留在细胞膜上。尽管编码抗原的定位存在差异，但编码主要或中间蛋白的质粒在接种动物中仍产生相似的抗体和T细胞增殖反应。在融合或非融合背景下共表达IL-2和包膜蛋白的质粒的使用导致增强的体液和细胞免疫应答。另外，通过IL-2的共表达，疫苗的免疫效力按剂量增加至少100倍。我们还发现，共表达IL-2的DNA疫苗有助于克服主要的组织相容性复合物对HBsAg疫苗的无反应性。 HBV DNA疫苗引起的免疫应答也通过IL-2的共表达而得到调节。当在体外用抗原再刺激时，接受共表达IL-2和包膜蛋白的小鼠的脾细胞产生的T辅助1（Th1）样应答要强于仅注射编码包膜蛋白的质粒的小鼠。 。 IL-2的共表达也增加了Th2样反应，尽管这种增加的意义不大。

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