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

Shuo Liu; Yan Zhao; Linpei Guo; Qilin Yu

doi:10.1007/s12274-022-4809-1

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

Nano Res. 2023;16(1):938-950. doi: 10.1007/s12274-022-4809-1. Epub 2022 Sep 2.

Authors

Shuo Liu^{1

2

3}, Yan Zhao¹, Linpei Guo⁴, Qilin Yu^{1

2}

Affiliations

¹ Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, 300071 China.
² Research Center for Infectious Diseases, Nankai University, Tianjin, 300350 China.
³ College of Environmental Science and Engineering, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, Nankai University, Tianjin, 300350 China.
⁴ Department of Urology, The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, 214002 China.

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.

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.

Keywords: dextran; engineered protein; magnetic nanoparticle; microgel; systemic infection; vaccination.