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首页> 外文期刊>Allergy >Novel cytokine peptide-based vaccines: an interleukin-4 vaccine suppresses airway allergic responses in mice.
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Novel cytokine peptide-based vaccines: an interleukin-4 vaccine suppresses airway allergic responses in mice.

机译：基于细胞因子肽的新型疫苗：白介素4疫苗可抑制小鼠的气道过敏反应。

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Background: Monoclonal antibodies or soluble receptors have been used to block over-produced endogenous cytokines. However, they have disadvantages of short half-lives, high costs, and possible adverse effects. Using interleukin (IL)-4 as a model target, we sought to develop a novel therapeutic strategy by constructing an IL-4 peptide-based vaccine for blocking IL-4 on a persistent basis, and to evaluate its efficacy in a mouse model of asthma. Methods: A peptide was selected by antigenic prediction and structure analysis of IL-4/receptor complex. The vaccine was constructed by employing truncated hepatitis B core antigen as carrier with the peptide inserted using gene engineering methods. It was then expressed, purified and identified. Prior to intraperitoneal sensitization and intranasal challenge with ovalbumin, mice were subcutaneously immunized three times with the vaccine, or the carrier or saline as controls. Serum antibodies, inflammatory cells in bronchoalveolar lavage fluids (BALF), lung histology, and responsiveness to inhaled methacholine were analyzed. Results: The vaccine presented as virus-like particles and reacted to polyclonal anti-IL-4 in Western blotting. Vaccinated mice produced high titers of IgG to IL-4. Serum ovalbumin-specific IgE, eosinophil accumulation in BALF, goblet cell hyperplasia, tissue inflammation and methacoline-induced respiratory responses were markedly suppressed in vaccinated mice with statistical significance, as compared with those in the control groups. Conclusions: Administration of this novel IL-4 vaccine led to an overall decrease in the development of airway allergic inflammatory responses. The results indicate that cytokine peptide-based vaccines hold potential for treatment of asthma and, by extension, other diseases where over-expressed cytokines play a pivotal role in pathogenesis.
机译：背景：单克隆抗体或可溶性受体已被用来阻断过度产生的内源性细胞因子。但是，它们具有半衰期短，成本高以及可能产生不利影响的缺点。我们以白介素（IL）-4为模型靶标，试图通过构建基于IL-4肽的疫苗来持续阻断IL-4来开发一种新型治疗策略，并评估其在小鼠模型中的功效。哮喘。方法：通过IL-4 /受体复合物的抗原预测和结构分析选择一种肽。通过使用截短的乙型肝炎核心抗原作为载体并使用基因工程方法插入肽来构建疫苗。然后将其表达，纯化和鉴定。在用卵清蛋白进行腹膜内致敏和鼻内攻击之前，用疫苗或载体或生理盐水作为对照皮下免疫小鼠3次。分析血清抗体，支气管肺泡灌洗液（BALF）中的炎性细胞，肺组织学以及对吸入的乙酰甲胆碱的反应性。结果：该疫苗呈病毒样颗粒，在Western印迹中与多克隆抗IL-4反应。接种疫苗的小鼠产生针对IL-4的高滴度的IgG。与对照组相比，接种疫苗的小鼠的血清卵清蛋白特异性IgE，嗜酸性粒细胞在BALF中的蓄积，杯状细胞增生，组织炎症和美沙可林诱导的呼吸道反应均得到了显着抑制，具有统计学意义。结论：这种新型IL-4疫苗的使用导致气道过敏性炎症反应的发展总体上减少。结果表明，基于细胞因子肽的疫苗具有治疗哮喘的潜力，并具有扩展性，可用于其他疾病，其中过表达的细胞因子在发病机理中起关键作用。

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