Biomineralization-Inspired Manganese Phosphate-Based Nanovaccine: Fabrication and in vitro Immunological Application

Conventional vaccines, particularly those formulated with aluminum salt adjuvants, are ineffective at inducing cellular immunity, limiting the therapeutic efficacy of tumor vaccines. Herein, using ovalbumin (OVA) as a template, an OVA-loaded manganese phosphate nanovaccine (OVA@MnP) was constructed via a biomineralization strategy. The nanovaccine was systematically characterized by TEM, SEM, and XPS, confirming its well-defined morphology and elemental composition. OVA@MnP exhibited excellent physiological stability and pH-responsive release behavior, enabling triggered antigen and Mn²⁺ release in acidic environments. Cellular uptake and lysosomal escape were confirmed using fluorophore-conjugated OVA@MnP-FITC in DC2.4 cells. Upon cytosolic entry, released Mn²⁺ enhanced cGAS sensitivity, significantly upregulating STING and pSTING levels and potently activating the cGAS-STING pathway. This activation increased bone marrow-derived dendritic cells (BMDCs) maturation by 2.41-fold and elevated the M1/M2 macrophage ratio by 7.54-fold, effectively inducing antigen-specific cellular immune responses. In summary, OVA@MnP represents a promising tumor vaccine candidate, offering a novel strategy for cancer immunotherapy.