STING agonist-loaded mesoporous manganese-silica nanoparticles for vaccine applications

Cyclic dinucleotides (CDNs), as one type of Stimulator of Interferon Genes (STING) pathway agonist, have shown promising results for eliciting immune responses against cancer and viral infection. However, the suboptimal drug-like properties of conventional CDNs, including their short in vivo half-life and poor cellular permeability, compromise their therapeutic efficacy. In this study, we have developed a manganese-silica nanoplatform (MnO_x@HMSN) that enhances the adjuvant effects of CDN by achieving synergy with Mn²⁺ for vaccination against cancer and SARS-CoV-2. MnO_x@HMSN with large mesopores were efficiently co-loaded with CDN and peptide/protein antigens. MnO_x@HMSN(CDA) amplified the activation of the STING pathway and enhanced the production of type-I interferons and other proinflammatory cytokines from dendritic cells. MnO_x@HMSN(CDA) carrying cancer neoantigens elicited robust antitumor T-cell immunity with therapeutic efficacy in two different murine tumor models. Furthermore, MnO_x@HMSN(CDA) loaded with SARS-CoV-2 antigen achieved strong and durable (up to one year) humoral immune responses with neutralizing capability. These results demonstrate that MnO_x@HMSN(CDA) is a versatile nanoplatform for vaccine applications.