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首页> 美国卫生研究院文献>Human Vaccines Immunotherapeutics >Sequential administration of cytokine genes to enhance cellular immune responses and CD4+ T memory cells during DNA vaccination
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Sequential administration of cytokine genes to enhance cellular immune responses and CD4+ T memory cells during DNA vaccination

机译：在DNA疫苗接种过程中顺序施用细胞因子基因以增强细胞免疫应答和CD4 + T记忆细胞

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Antigen specific memory T cells (Tm) have shown to be an important factor in protecting hosts against subsequent infection by previously encountered pathogens. During T-cell activation, several cytokines including IL-6, IL-7 and IL-15, play crucial roles in the development of T cells into memory T cells. With the aim of generating specific Tm, we examined a strategy of sequential administration of molecular adjuvants. In this strategy a DNA vaccine encoding the VP1 capsid protein of foot and mouth disease virus (designated pcD-VP1) was co-delivered to mice along with an IL-6 expressing plasmid (pVAX-IL-6) as an initial molecular adjuvant and boosted with either an IL-7 or IL-15 expressing plasmid, (pVAX-IL-7 or proVAX-IL-15) as the secondary adjuvant. During the pcD-VP1 immunization, we demonstrated that the groups primed with IL-6 and boosted with either IL-7 or IL-15 resulted in the enhancement of cellular and humoral immune responses, maturation of dendritic cells (DCs) and macrophages, and a higher frequency of CD4+ Tm (characterized by expressing CD44highCD62Llow markers, compared with the other groups). Thus, we took advantage of the different effects of cytokines on T cell development, not only to induce a higher level of immune responses after vaccination, but also to generate a higher ratio of CD4+ Tm in this sequential cytokine prime-boost study. This would then lead to the mounting of an effective long-term antigen specific immune response.
机译：抗原特异性记忆T细胞（Tm）已证明是保护宿主免受先前遇到的病原体随后感染的重要因素。在T细胞活化过程中，包括IL-6，IL-7和IL-15在内的几种细胞因子在T细胞发育成记忆T细胞的过程中起着至关重要的作用。为了产生特定的Tm，我们研究了分子佐剂顺序给药的策略。在这种策略中，将编码口蹄疫病毒VP1衣壳蛋白的DNA疫苗（指定为pcD-VP1）与表达IL-6的质粒（pVAX-IL-6）一起作为初始分子佐剂共递送给小鼠。用表达IL-7或IL-15的质粒（pVAX-IL-7或proVAX-IL-15）增强作为辅助佐剂。在pcD-VP1免疫过程中，我们证明了用IL-6引发并用IL-7或IL-15增强的组可导致细胞和体液免疫应答增强，树突状细胞（DC）和巨噬细胞成熟，以及CD4 + Tm的频率更高（与其他组相比，通过表达CD44 high CD62L low 标记来表征）。因此，我们利用了细胞因子对T细胞发育的不同影响，不仅在疫苗接种后诱导了更高水平的免疫反应，而且在此顺序中产生了更高比例的CD4 + Tm细胞因子初免-升压研究。然后，这将导致建立有效的长期抗原特异性免疫应答。

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