Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, Canada.
Allergy. 2011 Jun;66(6):784-91. doi: 10.1111/j.1398-9995.2011.02610.x. Epub 2011 Apr 20.
Specific allergen immunotherapy is clinically effective and disease modifying. It has a duration of effect that exceeds the treatment period and prevents both the progression of allergic rhinitis to asthma and the acquisition of new allergic sensitizations. However, immunotherapy is associated with a high frequency of adverse events related to the allergenicity of vaccines. Allergenicity is conferred by the presence of intact B-cell epitopes that crosslink allergen-specific IgE on effector cells. The use of linear peptide sequences representing fragments of the native allergen is one approach to reduce allergenicity. Preclinical models of peptide immunotherapy have demonstrated efficacy in both autoimmunity and allergy. Translation of this technology into the clinic has gained momentum in recent years based on encouraging results from early clinical trials. To date, efforts have focused on two major allergens, but vaccines to a broader range of molecules are currently in clinical development. Mechanistically, peptide immunotherapy appears to work through the induction of adaptive, allergen-specific regulatory T cells that secrete the immunoregulatory cytokine IL-10. There is also evidence that peptide immunotherapy targeting allergen-specific T cells can indirectly modulate allergen-specific B-cell responses. Peptide immunotherapy may provide a safe and efficacious alternative to conventional subcutaneous and/or sublingual approaches using native allergen preparations.
特异性变应原免疫疗法具有临床疗效和疾病改善作用。它的作用持续时间超过治疗期,可预防过敏性鼻炎发展为哮喘和新的变应原致敏。然而,免疫疗法与疫苗的变应原性相关的不良反应发生率高。变应原性是由交联效应细胞上的过敏原特异性 IgE 的完整 B 细胞表位赋予的。使用代表天然过敏原片段的线性肽序列是降低变应原性的一种方法。肽免疫疗法的临床前模型已在自身免疫和过敏中证明了疗效。基于早期临床试验的令人鼓舞的结果,近年来,该技术向临床应用的转化取得了进展。迄今为止,研究工作主要集中在两种主要过敏原上,但目前正在开发针对更广泛分子的疫苗。从机制上讲,肽免疫疗法似乎通过诱导适应性、过敏原特异性调节性 T 细胞来发挥作用,这些细胞分泌免疫调节细胞因子 IL-10。还有证据表明,针对过敏原特异性 T 细胞的肽免疫疗法可以间接调节过敏原特异性 B 细胞反应。与使用天然过敏原制剂的传统皮下和/或舌下方法相比,肽免疫疗法可能是一种安全有效的替代方法。