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一种涂覆有层状双氢氧化物的仿生酵母壳疫苗可诱导针对肿瘤的强大体液免疫和细胞免疫反应。

A biomimetic yeast shell vaccine coated with layered double hydroxides induces a robust humoral and cellular immune response against tumors.

作者信息

Liu Dong-Qun, Lu Shuai, Zhang Lun, Zhang Ling-Xiao, Ji Mei, Liu Xiao-Ge, Yu Zhuo, Liu Rui-Tian

机构信息

National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences Haidian District Beijing 100190 China

School of Chemical Engineering, University of Chinese Academy of Science Beijing 100049 China.

出版信息

Nanoscale Adv. 2020 Jun 26;2(8):3494-3506. doi: 10.1039/d0na00249f. eCollection 2020 Aug 11.

Abstract

Enhancing both the humoral and cellular immune response for tumor vaccination remains a challenge. Inspired by natural pathogen structures, we took β-glucan particles derived from a baker's yeast cell shell (YS) as a vaccine carrier and danger signal for dendritic cells (DCs), and coated the YS with catanionic layered double hydroxides (LDH) by electrostatic adsorption to form a biomimetic yeast cell particle (YSL). Our experimental results showed that the YSL vaccine efficiently targeted antigen-presenting cells (APCs) and remarkably enhanced antigen cross-presentation, and strongly improved the activation and maturation of DCs. Moreover, the YSL vaccine elicited an extremely high antibody titer and strong antigen-specific cytotoxic T lymphocyte together with mixed Th1/Th17 cellular immune responses and induced marked prophylactic and therapeutic effects against E.G7-OVA tumors in mouse models. These results suggest that YSL, integrating a yeast shell to mimic natural pathogens and LDH with high antigen-loading capacity and lysosome escape, is a promising tumor vaccine platform for rapid, effective and strong induction of both humoral and cellular immune responses.

摘要

增强肿瘤疫苗接种的体液免疫和细胞免疫反应仍然是一项挑战。受天然病原体结构的启发,我们采用源自面包酵母细胞壁(YS)的β-葡聚糖颗粒作为疫苗载体和树突状细胞(DCs)的危险信号,并通过静电吸附将YS与阴阳离子层状双氢氧化物(LDH)包覆,形成仿生酵母细胞颗粒(YSL)。我们的实验结果表明,YSL疫苗有效地靶向抗原呈递细胞(APC),显著增强抗原交叉呈递,并强烈促进DCs的激活和成熟。此外,YSL疫苗引发了极高的抗体滴度和强烈的抗原特异性细胞毒性T淋巴细胞,以及混合的Th1/Th17细胞免疫反应,并在小鼠模型中对E.G7-OVA肿瘤产生了显著预防和治疗效果。这些结果表明,YSL整合了模拟天然病原体的酵母外壳和具有高抗原负载能力及溶酶体逃逸能力的LDH,是一个有前景的肿瘤疫苗平台,可快速、有效且强烈地诱导体液免疫和细胞免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f2/9419453/eec847978da3/d0na00249f-f1.jpg

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