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Adjuvant-free nanofiber vaccine induces in situ lung dendritic cell activation and TH17 responses

机译:佐剂的纳米纤维疫苗诱导原位肺树突细胞活化和Th17响应

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The current paradigm that subunit vaccines require adjuvants to optimally activate innate immunity implies that increased vaccine reactogenicity will invariably be linked to improved immunogenicity. Countering this paradigm, nanoparticulate vaccines have been reported to act as delivery systems for vaccine antigens and induce immunity without the need for exogenous adjuvants or local inflammation; however, the mechanisms underlying the immunogenicity of nanoparticle vaccines are incompletely identified. Here, we show that antigens displayed on self-assembling nanofiber scaffolds and delivered intranasally are presented by CD103sup+/sup and CD11bsup+/sup lung dendritic cells that up-regulate CD80 and migrate into the draining lymph node (LN). This was accompanied by a nearly exclusive priming and accumulation of antigen-specific TsubH/sub17 cells occurring independently in both LN and lung. Thus, self-assembling peptide nanofiber vaccines may represent a novel, needle- and adjuvant-free means of eliciting protective immunity against fungal and bacterial infections at skin and mucosal barrier surfaces.
机译:亚基疫苗需要佐剂以最佳地激活先天免疫的目前的范例意味着增加的疫苗反应发生性将总是与改善的免疫原性相关联。据报道,对抗该范式,纳米颗粒疫苗作为疫苗抗原的递送系统,诱导免疫,而无需外源佐剂或局部炎症;然而,纳米颗粒疫苗免疫原性的机制是不完全鉴定的。在这里,我们表明,在自组装纳米纤维支架上显示的抗原和鼻内递送的CD103 + 和CD11b + / sup>肺树突细胞,其上调CD80并迁移到排水淋巴结(LN)。这伴随着抗原特异性T h 17细胞的几乎专用的初步和积累,在LN和肺中独立地发生。因此,自组装肽纳米纤维疫苗可以代表一种新的,针和佐剂的免疫性免受皮肤和粘膜阻挡表面的真菌和细菌感染的保护性免疫感。

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