Enhancing Dendritic Cell Activation Through Manganese-Coated Nanovaccine Targeting the cGAS-STING Pathway

Background: Nanovaccines have emerged as a promising vaccination strategy, exhibiting their capacity to deliver antigens and adjuvants to elicit specific immune responses. Despite this potential, optimizing the design and delivery of nanovaccines remains a challenge. Methods: In this study, we engineered a dendritic mesoporous silica-based nanocarrier enveloped in a metal-phenolic network (MPN) layer containing divalent manganese ions and tannic acid (MSN@MT). This nanocarrier was tailored for antigen loading to serve as a nanovaccine, aiming to activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway in dendritic cells (DCs). Our experimental approach encompassed both cellular assays and mouse immunizations, allowing a comprehensive evaluation of the nanovaccine's impact on DC activation and its influence on the generation of antigen-specific T-cell responses. Results: MSN@MT demonstrated a remarkable enhancement in humoral and cellular immune responses in mice compared to control groups. This highlights the potential of MSN@MT to effectively trigger the cGAS-STING pathway in DCs, resulting in robust immune responses. Conclusion: Our study introduces MSN@MT, a unique nanocarrier incorporating divalent manganese ions and tannic acid, showcasing its exceptional ability to amplify immune responses by activating the cGAS-STING pathway in DCs. This innovation signifies a stride in refining nanovaccine design for potent immune activation. Keywords: nanocarrier, metal-phenolic network, manganese ions, tannic acid