Long-Residence Pneumonia Vaccine Developed Using PEG-Grafted Hybrid Nanovesicles from Cell Membrane Fusion of Mycoplasma and IFN-gamma-Primed Macrophages
Zhang, ZZ (Zhang, Zhenzhen) 1Wang, HY (Wang, Haiyan) 1Xie, X (Xie, Xing) 1Chen, R (Chen, Rong) 1Li, J (Li, Jun) 1Ni, B (Ni, Bo) 1Yu, P (Yu, Pei) 2Liu, ZF (Liu, Zunfeng) 3Shao, GQ (Shao, Guoqing) 1Xiong, QY (Xiong, Qiyan) 1Wei, YN (Wei, Yanna) 1Liu, BB (Liu, Beibei) 1Feng, ZX (Feng, Zhixin) 1Zhou, X (Zhou, Xiang) 4Zhang, C (Zhang, Chao) 2
SMALL, 2021, Article Number 2101183
DOI 10.1002/smll.202101183
Abstract
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.
