Abstract:
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 Trichoderma reesei cellobiohydrolases Cel6A and Cel7A, together with the sequence of the fluorescent protein mCherry. DexBP was further prepared by engineered Escherichia coli 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.
UNASSIGNED: 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 C. albicans 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.
摘要:
疫苗接种对于保护人群免受病原体感染至关重要。然而,其效率经常受到抗原保留和呈递失败的影响。在这里,我们设计了一种葡聚糖结合蛋白DexBP,它由里氏木霉纤维二糖水解酶Cel6A和Cel7A的碳水化合物结合结构域组成,连同荧光蛋白mCherry的序列。通过工程大肠杆菌细胞进一步制备DexBP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)框架和活性氧响应接头整合,获得用于携带病原体抗原的磁性聚合物微凝胶。类似于变形虫聚集,微凝胶自组装形成聚集体并进一步诱导树突状细胞聚集。这种逐步组装在淋巴结保留了抗原,促进抗原呈递,刺激的体液免疫,并保护小鼠免受危及生命的全身感染。这项研究开发了一个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。
未经授权:补充材料(MG的AFM图像和zeta电位;TEM,FT-IR,DLS,MNP-DexBP的zeta电位;MG+CaAg和MG+MNP-DexBP+CaAg的zeta电位;MG+CaAg和MG+MNP-DexBP+CaAg的抗原释放谱;MG+MNP-DexBP+CaAg诱导的树突状细胞的聚集和分散;FITC标记的CaAg的摄取和抗树突状细胞抗原活化后第3天和对照抗体在树突状CaAg,MG+CaAg,和MG+MNP-DexBP+CaAg)可在本文的在线版本中获得,网址为10.1007/s12274-022-4809-1。