Zeolitic Imidazolate Frameworks Activate Endosomal Toll-like Receptors and Potentiate Immunogenicity of SARS-CoV-2 Spike Protein Trimer. Zeolitic Imidazolate Frameworks Activate Endosomal Toll-like Receptors and Potentiate Immunogenicity of SARS-CoV-2 Spike Protein Trimer

Nanomaterials offer new opportunities to engineer immunomodulatory activity. In this work, we report the endosomal toll-like receptor agonist activity of a nanoscale adjuvant zeolitic imidazolate frameworks-8 (ZIF-8). The accumulation of ZIF-8 in endosomes and the pH-responsive release of its subunits enable selective engagement with endosomal TLRs, minimizing the risk of off-target activation. The intrinsic adjuvant properties of ZIF-8, along with the efficient delivery and biomimetic presentation of a SARS-CoV-2 spike protein receptor binding domain trimer, primed rapid humoral and cell mediated immunity in a dose sparing manner. Our study offers new insights for next-generation adjuvants that can potentially impact future vaccine development. Overall design: Gene expression comparisons of 3 replicates each of lymph node RNA extracted from mice immunized with RBD-trimer, ZIF-8 or GR-ZIF compared with PBS controls.

纳米材料为免疫调节活性的工程化构建提供了全新契机。本研究报道了纳米级佐剂沸石咪唑酯骨架材料-8（zeolitic imidazolate frameworks-8，ZIF-8）的内体Toll样受体激动剂活性。ZIF-8在内体中的蓄积及其亚基的pH响应释放，使其可选择性结合内体Toll样受体，从而降低脱靶激活的风险。ZIF-8固有的佐剂特性，结合对新型冠状病毒（SARS-CoV-2）刺突蛋白受体结合域三聚体的高效递送与仿生呈递，可通过节省剂量的方式快速诱导体液免疫与细胞介导免疫。本研究为下一代佐剂的开发提供了全新见解，有望对未来疫苗研发产生积极影响。实验整体设计：对分别经RBD三聚体、ZIF-8或GR-ZIF免疫的小鼠所提取的淋巴结RNA各3个生物学重复样本，与磷酸盐缓冲液（phosphate buffered saline，PBS）对照组进行基因表达差异比较。