Amoeba-inspired magnetic microgel assembly assisted by engineered dextran-binding protein for vaccination against life-threatening systemic infection

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. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: 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.