Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada; Department of Immunology, University of Manitoba, Winnipeg, Canada.
Clin Exp Allergy. 2012 Sep;42(9):1397-405. doi: 10.1111/j.1365-2222.2012.04022.x.
Studies have found that the IL-23/Th17 pathway plays an important role in the pathogenesis of atopic dermatitis (AD) and severe and steroid-resistant asthma. Targeting IL-23/Th17 pathway with monoclonal antibodies (mAb) has been successful in the reduction of skin and airway inflammation in animal models. However, the mAb has a short half-life, requiring repeated administrations. For the long-term suppression of IL-23/Th17 pathway, we have previously developed an IL-23p40 peptide-based virus-like particle vaccine, which induces long-lasting autoantibodies to IL-23.
We sought to evaluate the effects of this IL-23p40 peptide-based vaccine on the down-regulation of allergic skin and airway inflammation in mice.
Mice were subcutaneously injected three times with the IL-23p40 vaccine, or the vaccine carrier protein or saline as controls. Two weeks later, mice were epicutaneously sensitized with ovalbumin four times at a 2-week interval. One week after the final sensitization, mice were nasally administrated with ovalbumin daily for 3 days. One day later, bronchoalveolar lavage fluids (BALF), sera, lung and skin tissues were obtained and analysed.
Mice immunized with the vaccine produced high levels of IgG antibodies to IL-23, p40 and IL-12 that in vitro inhibited IL-23-dependent IL-17 production. The numbers of total cells, neutrophils, and eosinophils in BALF were significantly reduced in the vaccine group, compared with controls. The levels of IL-13, IL-5, IL-23 and, IL-17 in BALF and levels of serum ovalbumin-specific IgE, IgG1, and total IgE were also significantly decreased. Histological analysis showed less inflammation of the lung and skin tissues in the vaccine group, compared with controls.
Administration of an IL-23p40 peptide-based vaccine down-regulates allergic skin and airway inflammation, suggesting that this strategy may be a potential therapeutic approach in the treatment of AD and asthma.
研究发现，IL-23/Th17 通路在特应性皮炎（AD）和严重及类固醇耐药性哮喘的发病机制中发挥重要作用。用单克隆抗体（mAb）靶向 IL-23/Th17 通路已成功减少动物模型中的皮肤和气道炎症。然而，mAb 的半衰期较短，需要重复给药。为了长期抑制 IL-23/Th17 通路，我们之前开发了一种基于 IL-23p40 肽的病毒样颗粒疫苗，该疫苗可诱导针对 IL-23 的长效自身抗体。
我们旨在评估这种基于 IL-23p40 肽的疫苗对下调小鼠过敏皮肤和气道炎症的影响。
小鼠经皮下注射三次 IL-23p40 疫苗或疫苗载体蛋白或生理盐水作为对照。两周后，小鼠每隔两周经皮致敏卵清蛋白四次。最后一次致敏后一周，每日经鼻给予卵清蛋白 3 天。一天后，获取支气管肺泡灌洗液（BALF）、血清、肺和皮肤组织并进行分析。
接种疫苗的小鼠产生高水平的 IgG 抗体，可体外抑制 IL-23 依赖性 IL-17 产生，针对 IL-23、p40 和 IL-12。与对照组相比，疫苗组 BALF 中的总细胞、中性粒细胞和嗜酸性粒细胞数量显著减少。BALF 中的 IL-13、IL-5、IL-23 和 IL-17 以及血清卵清蛋白特异性 IgE、IgG1 和总 IgE 水平也显著降低。组织学分析显示，与对照组相比，疫苗组的肺和皮肤组织炎症较少。
给予基于 IL-23p40 肽的疫苗可下调过敏皮肤和气道炎症，表明该策略可能是治疗 AD 和哮喘的潜在治疗方法。
Zotero 插件