Synthetic IgE peptide vaccine for immunotherapy of allergy.
Synthetic IgE peptide vaccine for immunotherapy of allergy.
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用于过敏免疫治疗的合成 IgE 肽疫苗。
DOI：
10.1016/s0264-410x(02)00732-6
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发表时间：
2003
期刊：
影响因子：
5.5
通讯作者：
MacGlashan,DonaldW
中科院分区：
文献类型：
--
作者：
Wang,ChangYi;Walfield,AlanM;Fang,Xinde;Hammerberg,Bruce;Ye,John;Li,MingLie;Shen,Fan;Shen,Ming;Alexander,Valerie;MacGlashan,DonaldW
通过设计基于 IgE 的合成肽免疫原并选择其功能性免疫原性，生产了一种过敏免疫治疗疫苗。该疫苗通过主动免疫，靶向 IgE 上高亲和力受体 FcεRI 的结合位点。 IgE 重链上的肽靶位点选自 Cε2、Cε3 和 Cε4 结构域的氨基酸序列。通过表位作图研究对 IgE 的交叉反应性和功能性抗原性进行了表征。一种肽，从 Cε3 环区的 413-435 位进行修饰并受到构象限制，引发抗 IgE 抗体，阻止 IgE 介导的组胺释放。它通过与混杂的 T 辅助位点连接而产生免疫增强，产生完全合成的嵌合免疫原。该免疫原被证明可以诱导多克隆位点特异性抗 IgE 抗体，从而阻碍与 FcεRI 的结合，抑制 IgE 敏感的嗜碱性粒细胞释放组胺，抑制被动皮肤过敏反应，并且不发出脱粒信号。免疫犬的血清总 IgE 显着降低。
An immunotherapeutic vaccine for allergy was produced by designing IgE-based synthetic peptide immunogens and selecting them for functional immunogenicity. The vaccine targets the binding site on IgE for the high affinity receptor FcεRI, by active immunization. The peptide target site on IgE heavy chain was selected from among the amino acid sequences for the Cε2, Cε3, and Cε4 domains. These were characterised by epitope mapping studies for cross-reactivity to IgE and functional antigenicity. A peptide, modified from positions 413–435 of a loop region of Cε3 and subjected to conformational constraint, elicited anti-IgE antibodies that blocked IgE-mediated histamine release. It was immunopotentiated by linkage to a promiscuous T helper site to produce a wholly synthetic chimaeric immunogen. This immunogen was shown to induce polyclonal site-specific anti-IgE antibodies that obstruct binding to FcεRI, inhibit histamine release by IgE-sensitised basophils, inhibit passive cutaneous anaphylaxis, and do not signal degranulation. Immunized dogs experienced significant reductions in total serum IgE.