Liu Shuo, Zhao Yan, Guo Linpei, Yu Qilin
Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, 300071 China.
Research Center for Infectious Diseases, Nankai University, Tianjin, 300350 China.
Nano Res. 2023;16(1):938-950. doi: 10.1007/s12274-022-4809-1. Epub 2022 Sep 2.
Vaccination is critical for population protection from pathogenic infections. However, its efficiency is frequently compromised by a failure of antigen retention and presentation. Herein, we designed a dextran-binding protein DexBP, which is composed of the carbohydrate-binding domains of cellobiohydrolases Cel6A and Cel7A, together with the sequence of the fluorescent protein mCherry. DexBP was further prepared by engineered cells and grafted to magnetic nanoparticles. The magnetic nanoparticles were integrated with a dextran/poly(vinyl alcohol) framework and a reactive oxygen species-responsive linker, obtaining magnetic polymeric microgels for carrying pathogen antigen. Similar to amoeba aggregation, the microgels self-assembled to form aggregates and further induced dendritic cell aggregation. This step-by-step assembly retained antigens at lymph nodes, promoted antigen presentation, stimulated humoral immunity, and protected the mice from life-threatening systemic infections. This study developed a magnetic microgel-assembling platform for dynamically regulating immune response during protection of the body from dangerous infections.
Supplementary material (AFM image and zeta potential of MG; TEM, FT-IR, DLS, and zeta potential of MNP-DexBP; zeta potential of MG+CaAg and MG+MNP-DexBP+CaAg; antigen release profile of MG+CaAg and MG+MNP-DexBP+CaAg; aggregation and dispersion of dendritic cells induced by MG+MNP-DexBP+CaAg; uptake of FITC-labeled CaAg (fCaAg) and intracellular distribution of fCaAg in the dendritic cells; antigen retention and dendritic cell activation in lymph nodes; and serum anti-CaAg antibody levels on day 3 after infection in the mice pre-immunized by PBS (control), CaAg, MG+CaAg, and MG+MNP-DexBP+CaAg) is available in the online version of this article at 10.1007/s12274-022-4809-1.
疫苗接种对于保护人群免受病原体感染至关重要。然而,其效率常常因抗原保留和呈递失败而受到影响。在此,我们设计了一种葡聚糖结合蛋白DexBP,它由纤维二糖水解酶Cel6A和Cel7A的碳水化合物结合结构域以及荧光蛋白mCherry的序列组成。DexBP通过工程细胞进一步制备并接枝到磁性纳米颗粒上。磁性纳米颗粒与葡聚糖/聚乙烯醇框架和活性氧响应连接体整合,得到用于携带病原体抗原的磁性聚合物微凝胶。与变形虫聚集类似,微凝胶自组装形成聚集体,并进一步诱导树突状细胞聚集。这种逐步组装将抗原保留在淋巴结中,促进抗原呈递,刺激体液免疫,并保护小鼠免受危及生命的全身感染。本研究开发了一种磁性微凝胶组装平台,用于在保护身体免受危险感染期间动态调节免疫反应。
补充材料(微凝胶的原子力显微镜图像和zeta电位;MNP-DexBP的透射电子显微镜、傅里叶变换红外光谱、动态光散射和zeta电位;MG+CaAg和MG+MNP-DexBP+CaAg的zeta电位;MG+CaAg和MG+MNP-DexBP+CaAg的抗原释放曲线;MG+MNP-DexBP+CaAg诱导的树突状细胞的聚集和分散;FITC标记的CaAg(fCaAg)的摄取以及fCaAg在树突状细胞中的细胞内分布;淋巴结中的抗原保留和树突状细胞活化;以及在经PBS(对照)、CaAg、MG+CaAg和MG+MNP-DexBP+CaAg预免疫的小鼠感染后第3天的血清抗CaAg抗体水平)可在本文的在线版本中获取,链接为10.1007/s12274-022-4809-1。