鞭毛蛋白
免疫系统
纳米纤维
TLR5型
先天免疫系统
卵清蛋白
免疫增强剂
佐剂
材料科学
生物
细胞生物学
免疫学
受体
Toll样受体
纳米技术
生物化学
作者
Duo Fu,Mengjia Wang,Tao Yang,Min Li,Zhihui Liang,Chen Chen,Lei Zhang,Changying Xue,Bingbing Sun,Chuanbin Mao
出处
期刊:Biomaterials
[Elsevier]
日期:2022-09-01
卷期号:288: 121733-121733
被引量:8
标识
DOI:10.1016/j.biomaterials.2022.121733
摘要
Nanofibers are potential vaccines or adjuvants for vaccination at the mucosal interface. However, how their lengths affect the mucosal immunity is not well understood. Using length-tunable flagella (self-assembled from a protein termed flagellin) as model protein nanofibers, we studied the mechanisms of their interaction with mucosal interface to induce immune responses length-dependently. Briefly, through tuning flagellin assembly, length-controlled protein nanofibers were prepared. The shorter nanofibers exhibited more pronounced toll-like receptor 5 (TLR5) and inflammasomes activation accompanied by pyroptosis, as a result of cellular uptake, lysosomal damage, and mitochondrial reactive oxygen species generation. Accordingly, the shorter nanofibers elevated the IgA level in mucosal secretions and enhanced the serum IgG level in ovalbumin-based intranasal vaccinations. These mucosal and systematic antibody responses were correlated with the mucus penetration capacity of the nanofibers. Intranasal administration of vaccines (human papillomavirus type 16 peptides) adjuvanted with shorter nanofibers significantly elicited cytotoxic T lymphocyte responses, strongly inhibiting tumor growth and improving survival rates in a TC-1 cervical cancer model. This work suggests that length-dependent immune responses of nanofibers can be elucidated for designing nanofibrous vaccines and adjuvants for both infectious diseases and cancer.
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