Unit of Antibodies in Therapy and Pathology, Institut Pasteur, UMR 1222 INSERM, Paris, France.
Sorbonne University, ED394, Paris, France.
Nat Commun. 2021 May 11;12(1):2574. doi: 10.1038/s41467-021-22834-5.
Allergic asthma is characterized by elevated levels of IgE antibodies, type 2 cytokines such as interleukin-4 (IL-4) and IL-13, airway hyperresponsiveness (AHR), mucus hypersecretion and eosinophilia. Approved therapeutic monoclonal antibodies targeting IgE or IL-4/IL-13 reduce asthma symptoms but require costly lifelong administrations. Here, we develop conjugate vaccines against mouse IL-4 and IL-13, and demonstrate their prophylactic and therapeutic efficacy in reducing IgE levels, AHR, eosinophilia and mucus production in mouse models of asthma analyzed up to 15 weeks after initial vaccination. More importantly, we also test similar vaccines specific for human IL-4/IL-13 in mice expressing human IL-4/IL-13 and the related receptor, IL-4Rα, to find efficient neutralization of both cytokines and reduced IgE levels for at least 11 weeks post-vaccination. Our results imply that dual IL-4/IL-13 vaccination may represent a cost-effective, long-term therapeutic strategy for the treatment of allergic asthma as demonstrated in mouse models, although additional studies are warranted to assess its safety and feasibility.
变应性哮喘的特征是 IgE 抗体、2 型细胞因子（如白细胞介素-4 [IL-4] 和白细胞介素-13 [IL-13]）、气道高反应性（AHR）、黏液高分泌和嗜酸性粒细胞增多。针对 IgE 或 IL-4/IL-13 的已批准的治疗性单克隆抗体可减轻哮喘症状，但需要昂贵的终身给药。在这里，我们开发了针对小鼠 IL-4 和 IL-13 的偶联疫苗，并在哮喘小鼠模型中证明了它们在预防和治疗方面的功效，可降低 IgE 水平、AHR、嗜酸性粒细胞增多和黏液产生，分析时间最长可达初次接种后 15 周。更重要的是，我们还在表达人 IL-4/IL-13 及其相关受体 IL-4Rα 的小鼠中测试了针对人 IL-4/IL-13 的类似疫苗，发现两种细胞因子均可有效中和，且至少在接种后 11 周内 IgE 水平降低。我们的结果表明，双 IL-4/IL-13 疫苗可能代表一种具有成本效益的长期治疗策略，可用于治疗变应性哮喘，尽管还需要进行更多研究来评估其安全性和可行性。
