Tarzi M, Klunker S, Texier C, Verhoef A, Stapel S O, Akdis C A, Maillere B, Kay A B, Larché M
Department of Allergy and Clinical Immunology, Imperial College London, Faculty of Medicine, National Heart and Lung Institute, London, UK.
Clin Exp Allergy. 2006 Apr;36(4):465-74. doi: 10.1111/j.1365-2222.2006.02469.x.
Allergen-derived (T cell epitope) peptides may be safer for immunotherapy than native allergen, as they do not cross-link immunoglobulin (Ig)E. However, HLA polymorphism results in multiple potential epitopes. Synthetic peptides of phospholipase (PL) A(2) were selected for a peptide vaccine, on the basis of binding affinity for commonly expressed HLA-DR molecules.
To evaluate treatment with an HLA-DR-based PLA(2) peptide vaccine in subjects with mild honeybee allergy in an open, controlled study.
Twelve volunteers with allergy to bee venom received nine intradermal injections of PLA(2) peptides, with six untreated subjects serving as controls. Outcome was assessed by the size of the late-phase cutaneous reaction to allergen, peripheral blood mononuclear cell (PBMC) proliferation, cytokine release, and expression of genes associated with immune regulation.
Subjects receiving peptides showed a decrease in the magnitude of the late-phase cutaneous reaction to bee venom compared with controls (P=0.03). The proliferation of venom-stimulated PBMCs decreased in treated subjects compared with controls (P=0.01). Peptide treatment reduced the production of IL-13 by PLA(2)-stimulated PBMCs (P<0.01) and IFN-gamma (P<0.01), and increased the production of IL-10 (P=0.02). Transcription of the suppressor of cytokine signalling (Socs)3 gene was significantly increased following therapy. A transient, but modest, increase in allergen-specific IgG was also observed.
HLA-DR-based T cell epitopes modify surrogate markers associated with successful immunotherapy and induction of immune regulation, supporting the concept that this form of treatment may be efficacious in human allergic disease.
变应原衍生的（T细胞表位）肽对于免疫疗法而言可能比天然变应原更安全，因为它们不会交联免疫球蛋白（Ig）E。然而，HLA多态性会产生多种潜在表位。基于对常见表达的HLA-DR分子的结合亲和力，选择了磷脂酶（PL）A2的合成肽用于肽疫苗。
在一项开放、对照研究中评估基于HLA-DR的PLA2肽疫苗对轻度蜜蜂过敏受试者的治疗效果。
12名对蜂毒过敏的志愿者接受了9次PLA2肽皮内注射，6名未治疗的受试者作为对照。通过对变应原的迟发性皮肤反应大小、外周血单个核细胞（PBMC）增殖、细胞因子释放以及与免疫调节相关基因的表达来评估结果。
与对照组相比，接受肽治疗的受试者对蜂毒的迟发性皮肤反应程度降低（P = 0.03）。与对照组相比，治疗组中受毒液刺激的PBMC增殖减少（P = 0.01）。肽治疗降低了PLA2刺激的PBMC产生IL-13的水平（P < 0.01）和IFN-γ水平（P < 0.01），并增加了IL-10的产生（P = 0.02）。治疗后细胞因子信号传导抑制因子（Socs）3基因的转录显著增加。还观察到变应原特异性IgG有短暂但适度的增加。
基于HLA-DR的T细胞表位可改变与成功免疫疗法和免疫调节诱导相关的替代标志物，支持了这种治疗形式可能对人类过敏性疾病有效的概念。
