A Spleen-Targeted Tolerogenic mRNA-LNPs Vaccine for the Treatment of Experimental Asthma

IF 14.1 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Fazhan Wang, Jia Lou, Xiaohan Lou, Fang Wu, Xiaoke Gao, Xiaohan Yao, Jiajia Wan, Xixi Duan, Wenjing Deng, Lixia Ma, Lijing Zhang, Guangjie He, Ming Wang, Chen Ni, Ningjing Lei, Zhihai Qin
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Abstract

Lipid nanoparticles (LNPs)-based mRNA vaccines have witnessed their great advantages in the fight against infectious diseases. However, the pro-inflammatory properties of mRNA-LNPs vaccines may hinder the induction of antigen-specific tolerogenic immune responses. Here, it is demonstrated that stearic acid-doped LNPs co-loaded with nucleoside-modified mRNA and celastrol selectively target spleen, convert their adjuvanticity and promote a tolerogenic rather than immunogenic DCs phenotype. Furthermore, the tolerogenic mRNA vaccine also invokes the generation of antigen-specific regulatory T cells (Tregs) in the spleen and migration of the induced Tregs to the lung. In a mouse model of allergic asthma, immunization with the tolerogenic mRNA vaccine significantly alleviated symptom induction, reducing eosinophilic granulocyte accumulation and mucus secretion. In conclusion, this spleen-targeted mRNA-LNPs vaccine platform induces tolerogenic immune responses, offering promise for the development of therapeutics against allergic asthma and other conditions requiring immune tolerance modulation.

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脾脏靶向耐受原性mRNA-LNPs疫苗治疗实验性哮喘
基于脂质纳米颗粒(LNPs)的mRNA疫苗在对抗传染病方面具有巨大的优势。然而,mRNA-LNPs疫苗的促炎特性可能会阻碍抗原特异性耐受性免疫反应的诱导。本研究表明,硬脂酸掺杂的LNPs与核苷修饰的mRNA和雷公藤红素共载,选择性靶向脾脏,转化其佐剂性,促进耐受性而非免疫原性dc表型。此外,这种耐受原性mRNA疫苗还会在脾脏中产生抗原特异性调节性T细胞(Tregs),并将诱导的Tregs迁移到肺部。在小鼠变应性哮喘模型中,耐受原性mRNA疫苗免疫可显著缓解症状诱导,减少嗜酸性粒细胞积聚和粘液分泌。总之,这个脾脏靶向mRNA-LNPs疫苗平台诱导了耐受性免疫反应,为开发治疗过敏性哮喘和其他需要免疫耐受调节的疾病的疗法提供了希望。
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来源期刊
Advanced Science
Advanced Science CHEMISTRY, MULTIDISCIPLINARYNANOSCIENCE &-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
18.90
自引率
2.60%
发文量
1602
审稿时长
1.9 months
期刊介绍: Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.
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