Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Allergy. 2012 May;67(5):609-21. doi: 10.1111/j.1398-9995.2012.02794.x. Epub 2012 Feb 17.
More than 90% of house dust mite-allergic patients are sensitized to the major Dermatophagoides pteronyssinus allergen, Der p 2. The aim of this study was to develop and characterize an allergy vaccine based on carrier-bound Der p 2 peptides, which should allow reducing IgE- and T-cell-mediated side-effects during specific immunotherapy (SIT).
Five Der p 2 peptides (P1-P5) were synthesized and analyzed regarding IgE reactivity and allergenic activity. Lymphoproliferative and cytokine responses induced with Der p 2 and Der p 2 peptides were determined in peripheral blood mononuclear cells from mite-allergic patients. Der p 2-specific IgG antibodies induced with carrier-bound Der p 2 peptides in mice and rabbits were tested for their capacity to inhibit IgE binding and basophil activation in allergic patients.
Of five overlapping peptides (P1-P5) covering the Der p 2 sequence, two peptides (P2 and P4) were identified, which showed no relevant IgE reactivity, allergenic activity, and induced lower Der p 2-specific T-cell activation than Der p 2. However, when coupled to a carrier, P2 and P4 induced Der p 2-specific IgG antibodies in animals, which inhibited allergic patients' IgE binding to the allergen and allergen-induced basophil activation similar as antibodies induced with Der p 2.
Carrier-bound Der p 2 peptides should allow avoiding IgE-mediated side-effects, and because of their low potential to activate allergen-specific T cells, they may reduce late-phase side-effects during SIT. Further, these peptides may be also useful for prophylactic vaccination.
超过 90%的屋尘螨过敏患者对主要过敏原屋尘螨变应原 2(Der p 2)敏感。本研究旨在开发并鉴定基于载体结合 Der p 2 肽的变应原疫苗,以减少特异性免疫治疗(SIT)过程中 IgE 和 T 细胞介导的副作用。
合成了 5 个 Der p 2 肽(P1-P5),并对其 IgE 反应性和变应原活性进行了分析。从尘螨过敏患者的外周血单核细胞中测定 Der p 2 和 Der p 2 肽诱导的淋巴细胞增殖和细胞因子反应。在小鼠和兔中用载体结合的 Der p 2 肽诱导的 Der p 2 特异性 IgG 抗体,检测其在过敏患者中抑制 IgE 结合和嗜碱性粒细胞活化的能力。
在覆盖 Der p 2 序列的 5 个重叠肽(P1-P5)中,确定了 2 个肽(P2 和 P4),它们没有表现出明显的 IgE 反应性、变应原活性,并且诱导的 Der p 2 特异性 T 细胞活化低于 Der p 2。然而,当与载体结合时,P2 和 P4 在动物中诱导产生 Der p 2 特异性 IgG 抗体,这些抗体抑制过敏患者的 IgE 与过敏原结合,并抑制过敏原诱导的嗜碱性粒细胞活化,与用 Der p 2 诱导的抗体相似。
载体结合的 Der p 2 肽可以避免 IgE 介导的副作用,并且由于其激活过敏原特异性 T 细胞的潜力较低,它们可能会减少 SIT 过程中的迟发性副作用。此外,这些肽也可能对预防性疫苗接种有用。