BackgroundAnti‐IgE immunotherapy with monoclonal antibodies represents a breakthrough in treatment of severe allergic diseases. However, drawbacks such as short half‐life and high price are not negligible. Our objective is to develop an anti‐IgE vaccine based on virus‐like particles (VLPs) which can induce long‐lasting neutralizing IgG anti‐IgE antibodies reducing allergic responses without causing intrinsic mast cell activation due to IgE cross‐linking.MethodsThe vaccines were made by chemically coupling three synthetic mouse IgE‐Fc fragments to plant‐derived immunologically optimized CuMVTT VLPs. The immunogenicity of the vaccines was tested by immunizing naive or allergic mice either with the coupled vaccines or the VLP control followed by systemic or local allergen challenge.ResultsMice immunized with the vaccines exhibited high titers of anti‐IgE antibodies in the sera and high levels of anti‐IgE secreting plasma cells in lymphoid organs. Moreover, free IgE in serum were reduced by the induced anti‐IgE antibodies; therefore, less IgE was bound to FcεRI on the surface of basophils. In line with these reduced IgE levels on effector cells after vaccination, immunized mice were protected from challenge with allergens. Importantly, despite presence of anti‐IgE antibodies, no signs of acute or chronic allergic response were seen in immunized allergic mice.ConclusionThe generated vaccines can effectively induce anti‐IgE antibodies that did not cause allergic responses in sensitized mice but were able to decrease the level of free and cell bound IgE and protected sensitized animals from allergic responses upon allergen challenge.

中文翻译：

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生成基于病毒样颗粒的 IgE 疫苗

背景单克隆抗体抗 IgE 免疫治疗代表了严重过敏性疾病治疗的突破。然而，半衰期短、价格高等缺点也不容忽视。我们的目标是开发一种基于病毒样颗粒 (VLP) 的抗 IgE 疫苗，它可以诱导持久的中和 IgG 抗 IgE 抗体，减少过敏反应，而不会因 IgE 交联而引起内在肥大细胞激活。通过将三个合成的小鼠 IgE-Fc 片段与植物来源的免疫优化 CuMV 进行化学偶联而制成TTVLP。通过使用偶联疫苗或 VLP 对照对初始小鼠或过敏小鼠进行免疫，然后进行全身或局部过敏原攻击，测试了疫苗的免疫原性。结果用疫苗免疫的小鼠血清中表现出高滴度的抗 IgE 抗体和高水平的淋巴器官中分泌抗 IgE 的浆细胞。此外，诱导的抗 IgE 抗体减少了血清中的游离 IgE；因此，嗜碱性粒细胞表面与 FcεRI 结合的 IgE 较少。与接种疫苗后效应细胞上 IgE 水平降低一致，免疫小鼠免受过敏原的攻击。重要的是，尽管存在抗IgE抗体，但在免疫的过敏小鼠中没有观察到急性或慢性过敏反应的迹象。结论所产生的疫苗可以有效诱导抗IgE抗体，该抗体不会引起致敏小鼠的过敏反应，但能够降低过敏反应的发生率。游离和细胞结合 IgE 的水平，并保护致敏动物免受过敏原攻击后的过敏反应。