An AlFu MOF nanoadjuvant functionalized with mannose for potential dendritic-cell targeting and dual TLR9–STING activation

Aluminum adjuvants remain the most widely used adjuvants in licensed vaccines. Their broader application, however, is restricted by local and systemic adverse effects and limited antigen compatibility, slowing vaccine development.
A nanoscale aluminum – fumarate metal – organic framework (AlFu‑MOF) was synthesized in water using Pluronic F127 and acetic acid. Based on this framework, a composite nanoadjuvant—(D)-mannose‑cTAT‑CpG@M@AlFu‑MOF (DCC@M@AlFu‑MOF) – was designed and characterized. The loading capacity for immunostimulatory cargos, including MSA‑2, CpG, cTAT, (D)-mannose, and OVA, was evaluated. Cellular uptake and immune activation of antigen‑presenting cells were tested in vitro. AlFu‑MOF displayed high loading efficiency and improved antigen availability. DCC@M@AlFu‑MOF promoted dendritic cell maturation and activation and also triggered the STING signaling pathway.
DCC@M@AlFu‑MOF is an aluminum‑based nanoadjuvant with potential dendritic cell‑targeting ability. It can coordinate innate immune signaling and shows promise for enhancing vaccine‑induced immune responses.

铝佐剂仍是获批疫苗中应用最为广泛的佐剂。然而，其更广泛的应用受到局部与全身不良反应、抗原兼容性受限的制约，进而延缓了疫苗研发进程。
研究人员以泊洛沙姆F127（Pluronic F127）和乙酸为原料，在水相中合成了纳米级铝-富马酸金属有机框架（AlFu-MOF）。基于该框架，研究人员设计并表征了一种复合纳米佐剂——(D)-甘露糖-cTAT-CpG@M@AlFu-MOF（DCC@M@AlFu-MOF）。本研究评估了该复合佐剂对MSA-2、CpG、cTAT、(D)-甘露糖及卵清蛋白（OVA）等免疫刺激载荷的装载能力，并在体外检测了抗原呈递细胞的细胞摄取与免疫激活活性。结果表明，AlFu-MOF具备较高的装载效率与更优的抗原可及性；DCC@M@AlFu-MOF可促进树突状细胞的成熟与激活，同时能够激活STING信号通路（STING signaling pathway）。
DCC@M@AlFu-MOF是一种具备潜在树突状细胞靶向能力的铝基纳米佐剂，可协同调控先天免疫信号通路，在增强疫苗诱导的免疫应答方面展现出良好的应用前景。