Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV), Rue du Bugnon, Lausanne, 1011, Switzerland.
Clin Transl Allergy. 2013 Jun 1;3(1):17. doi: 10.1186/2045-7022-3-17.
Synthetic contiguous overlapping peptides (COPs) may represent an alternative to allergen extracts or recombinant allergens for allergen specific immunotherapy. In combination, COPs encompass the entire allergen sequence, providing all potential T cell epitopes, while preventing IgE conformational epitopes of the native allergen.
Individual COPs were derived from the sequence of Bet v 1, the major allergen of birch pollen, and its known crystal structure, and designed to avoid IgE binding. Three sets of COPs were tested in vitro in competition ELISA and basophil degranulation assays. Their in vivo reactivity was determined by intraperitoneal challenge in rBet v 1 sensitized mice as well as by skin prick tests in volunteers with allergic rhinoconjunctivitis to birch pollen.
The combination, named AllerT, of three COPs selected for undetectable IgE binding in competition assays and for the absence of basophil activation in vitro was unable to induce anaphylaxis in sensitized mice in contrast to rBet v 1. In addition no positive reactivity to AllerT was observed in skin prick tests in human volunteers allergic to birch pollen. In contrast, a second set of COPs, AllerT4-T5 displayed some residual IgE binding in competition ELISA and a weak subliminal reactivity to skin prick testing.
The hypoallergenicity of contiguous overlapping peptides was confirmed by low, if any, IgE binding activity in vitro, by the absence of basophil activation and the absence of in vivo induction of allergic reactions in mouse and human.
ClinicalTrials.gov NCT01719133.
合成连续重叠肽（COPs）可能是变应原提取物或重组变应原的替代物，用于变应原特异性免疫治疗。COPs 联合使用涵盖了整个变应原序列，提供了所有潜在的 T 细胞表位，同时防止了天然变应原的 IgE 构象表位。
从桦树花粉的主要变应原 Bet v 1 的序列及其已知晶体结构中衍生出单个 COPs，并设计为避免 IgE 结合。在竞争 ELISA 和嗜碱性粒细胞脱颗粒测定中，测试了三组 COPs 的体外反应。通过 rBet v 1 致敏小鼠的腹腔内挑战以及对桦树花粉过敏的变应性鼻炎结膜炎志愿者的皮肤点刺试验来确定其体内反应性。
组合名为 AllerT 的三种 COPs 选择用于竞争测定中不可检测的 IgE 结合和体外无嗜碱性粒细胞活化，与 rBet v 1 相比，不能在致敏小鼠中诱导过敏反应。此外，在对桦树花粉过敏的人类志愿者的皮肤点刺试验中，未观察到对 AllerT 的阳性反应。相比之下，第二组 COPs，AllerT4-T5 在竞争 ELISA 中显示出一些残留的 IgE 结合活性和对皮肤点刺测试的微弱亚阈值反应性。
通过体外低（如果有的话）IgE 结合活性、无嗜碱性粒细胞活化以及在小鼠和人类中无体内诱导过敏反应，证实了连续重叠肽的低变应原性。
ClinicalTrials.gov NCT01719133。
