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A Spleen‐Targeted Tolerogenic mRNA‐LNPs Vaccine for the Treatment of Experimental Asthma
https://orcid.org/0000-0001-9793-7964
AbstractLipid 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.
A Spleen‐Targeted Tolerogenic mRNA‐LNPs Vaccine for the Treatment of Experimental Asthma
https://orcid.org/0000-0001-9793-7964
AbstractLipid 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.
A Spleen‐Targeted Tolerogenic mRNA‐LNPs Vaccine for the Treatment of Experimental Asthma
https://orcid.org/0000-0001-9793-7964
AbstractLipid 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.
A Spleen‐Targeted Tolerogenic mRNA‐LNPs Vaccine for the Treatment of Experimental Asthma
Advanced Science
Wang, Fazhan (author) / Lou, Jia (author) / Lou, Xiaohan (author) / Wu, Fang (author) / Gao, Xiaoke (author) / Yao, Xiaohan (author) / Wan, Jiajia (author) / Duan, Xixi (author) / Deng, Wenjing (author) / Ma, Lixia (author)
2025-02-08
Article (Journal)
Electronic Resource
English
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