DUMP Cascade-Oriented MnOx@MSN Nanoadjuvant for Subunit Vaccine Antigen Delivery and Immune Potentiation

Abstract

Induction of immunity by protein-antigen subunit vaccines requires sequential completion of lymph node drainage, dendritic cell (DC) uptake, DC maturation, and antigen cross-presentation, collectively termed the DUMP cascade. Effective lymph node drainage and efficient antigen uptake by DCs are the core upstream prerequisites for the DUMP cascade initiation, and they are the limiting steps in the early stage that determine the efficiency of immune activation. The traditional mesoporous silica nanomaterials (MSNs) have limitations such as large particle size and lack of immune stimulation. Therefore, developing a carrier system to enhance immune response remains a key challenge for improving the efficacy of subunit vaccines. In this study, we constructed a small MnOx@MSNs nanoplatform by modifying the MSN surface with MnOx, leveraging its capacity to drain to lymph node and ion stimulation. Characterization confirmed that the system retained a sub-100 nm hydrodynamic diameter and an ordered mesoporous architecture while exhibiting enhanced Mn ion release under an acidic or reductive microenvironment. Cell experiments demonstrated that MnOx@MSNs preserved favorable cytocompatibility while simultaneously enhancing antigen uptake, elevating intracellular reactive oxygen species (ROS) levels, and upregulating the expression of immune-related genes including CXCL10, IL-12B, IL-6, IFN-β1, IFIT1, and CCL2. In vivo studies further demonstrated improved antigen transport to draining lymph nodes and strengthened antigen-specific IgG responses. This work provides a materials-design strategy and experimental basis, offering a promising route toward more potent subunit vaccines.