Multi-signaling pathway activation by pH responsive manganese particles for enhanced vaccination

As metal ions play important roles in the process of immunomodulation, immunotherapy based on metal ions has attracted tremendous interests in recent years. Here, we screened common metal ions and found that Mn²⁺ could enhance the immune function in vitro. A new type of nanovaccine is thus fabricated by a biomimetic approach using nanoscale coordination polymer formed by Mn²⁺ and 2-methylimidazole (2-MI) to encapsulate ovalbumin (OVA) protein, a model antigen, obtaining OVA@MM nanoparticles. Compared to free OVA, OVA@MM nanoparticles could more effectively induce the maturation of bone marrow-derived dendritic cells (BMDCs) and their subsequent antigen cross-presentation. The particles made of Mn²⁺ and 2-MI could activate immune-regulated signal pathways to enhance the immune functions of BMDCs. Such OVA@MM nanovaccine could not only provide prophylactic effect to inhibit the growth of B16-OVA tumor on immunized mice, but also significantly inhibit tumor growth in the mice with B16-OVA tumor combined with anti-programmed cell death protein 1 (anti-PD-1) antibody. Therefore, this nanovaccine platform based on Mn²⁺, 2-MI and antigen may provide a simple, effective and broadly applicable strategy to enhance adaptive immunity against cancer and other diseases.