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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

作者: Zhang, Zhenzhen 1 ; Wang, Haiyan 1 ; Xie, Xing 1 ; Chen, Rong 1 ; Li, Jun 1 ; Ni, Bo 1 ; Yu, Pei 2 ; Liu, Zunfeng 3 ; Shao, 1 ;

作者机构: 1.Jiangsu Acad Agr Sci, Inst Vet Med, Nanjing 210014, Peoples R China

2.China Pharmaceut Univ, Sch Tradit Chinese Pharm, Nanjing 210009, Peoples R China

3.Nankai Univ, State Key Lab Med Chem Biol, Key Lab Funct Polymer Mat, Coll Pharm, Tianjin 300071, Peoples R China

4.China Pharmaceut Univ, Dept Sci, Nanjing 211198, Peoples R China

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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