题目: | Inhalable Respiratory Driven Penetration of Porous Microsphere-Based Mucosal Vaccine for Long-Term Immune Protection |
作者: | Zhisheng Xiao1,2,3, Zhiqiang Wu1, Qiaofeng Li2, Jiafei Zhu2, Bo Liu2, Yu Miao2, Yifan Yang2, Junjie Zhu1, Linfu Chen2, Boxiong Bai2, Feng Pan1, Yang Yang1,3*, Qian Chen2* |
单位: | 1Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China. 2Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, China. 3Department of Thoracic Surgery, The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. |
摘要: | Inhalable mucosal vaccines elicit mucosal immunity non-invasively but are hindered by lung barriers like mucociliary clearance and phagocytosis, which typically necessitate multiple doses. Herein, we developed an innovative inhalable porous microsphere (pMS) vaccine using a single Food and Drug Administration-approved material, featuring a dual-scale design: an aerodynamic diameter of 4.84 µm for optimal deep lung deposition and a geometric size of 14.7 µm to evade phagocytosis for long-term retention. Notably, respiratory motion facilitates the penetration of pMS through the mucus layer into the pulmonary interstitium, where it gradually releases antigens and adjuvants. Remarkably, a single inhalation induced durable immunity, sustaining high levels of IgG and IgA for one year, alongside enhancing tissue-resident memory T cells in the lung and promoting germinal center expansion in the lymph node. This provided long-term protective efficacy, significantly inhibiting lung tumor metastasis even a year after inhalation. Beyond prophylaxis, this vaccine demonstrated remarkable therapeutic efficacy across multiple preclinical models, including the in situ lung tumor model, postoperative recurrence prevention model, and clinically relevant Patient-Derived tumor Xenograft (PDX) model. The dry powder pMS platform is scalable, stable, and clinically translatable, emerging as a versatile therapeutic strategy to adapt to diverse Lung-related diseases. |
影响因子: | 26.8 |
分区情况: | 一区 |
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责任编辑:郭佳
