{"title":"A Spleen-Targeted Tolerogenic mRNA-LNPs Vaccine for the Treatment of Experimental Asthma","authors":"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","doi":"10.1002/advs.202412543","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":"12 13","pages":""},"PeriodicalIF":14.1000,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/advs.202412543","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Science","FirstCategoryId":"88","ListUrlMain":"https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202412543","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
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.
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.