Long-Residence Pneumonia Vaccine Developed Using PEG-Grafted Hybrid Nanovesicles from Cell Membrane Fusion of Mycoplasma and IFN-gamma-Primed Macrophages

文献类型： 外文期刊

第一作者： Zhang, Zhenzhen

作者： Zhang, Zhenzhen;Wang, Haiyan;Xie, Xing;Chen, Rong;Li, Jun;Ni, Bo;Shao, Guoqing;Xiong, Qiyan;Wei, Yanna;Liu, Beibei;Feng, Zhixin;Yu, Pei;Zhang, Chao;Liu, Zunfeng;Zhou, Xiang

作者机构：

关键词： CD8; (+) T cell responses; cell membrane fusion; hybrid nanovesicles; macrophages; pneumonia vaccine

期刊名称：SMALL （ 影响因子：13.281； 五年影响因子：12.463 ）

ISSN： 1613-6810

年卷期： 2021 年 17 卷 34 期

页码：

收录情况： SCI

摘要： CD8(+) T cell responses play a critical regulatory role in protection against mycoplasma infection-related respiratory diseases. Nanovesicles derived from cell membranes have been shown to induce CD8(+) T cell responses. Moreover, the short residence time of mycoplasma membrane-related vaccines in local lymph nodes limits the efficacy of current mycoplasma vaccines. Here, a long-residence pneumonia vaccine is developed using nanovesicles prepared by cell membrane fusion of Mycoplasma hyopneumoniae and interferon-gamma (IFN-gamma -)-primed macrophages, which are grafted with polyethylene glycol to increase residence time in the lymph nodes. Upregulation of intercellular adhesion molecule-1 (ICAM-1) on the membrane of IFN-gamma-primed macrophages increases the targeting of the hybrid nanovesicle vaccine to the local lymph nodes, with increased CD8(+) T cell activation. A mechanistic study reveals that CD8(+) T cell activation is achieved via a pathway involving upregulation of C-C motif chemokine ligand 2/3 expression by E26 transformation-specific sequences, followed by increased immune-stimulatory activity of dendritic cells. In vivo, prophylactic testing reveals that the hybrid nanovesicle vaccine triggers a long-term immune response, as evidenced by a memory CD8(+) T cell response against mycoplasma infection. The current study provides a new design strategy for mycoplasma vaccines that involves a hybrid method using biological sources and artificial modification.

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