A precision-engineered dendritic cell-targeted mRNA nanovaccine for enhanced antiviral immunity
Shugang Qin, Qian Zheng, Yupei Zhang, Xinyang Jin, Xiangyu Jiao, Zhenyi Niu, Xi He, Xing Lan, Xing Duan, Chunli Yang, Xiaoling Yin, Shengbin Liu, Zhongshan He, Mengran Guo, Jiyan Liu, Xiangrong Song
Abstract
Messenger RNA (mRNA) vaccines have shown great therapeutic potential across multiple disease conditions, yet their success primarily depends on effective delivery strategies. Synthetic lipid-like nanoparticles (LLNs), leveraging biomimetic properties and adaptable surface chemistry, emerged as advanced vehicles for targeted mRNA vaccines with high efficacy and low toxicity. Here, we developed a dendritic cell (DC)-targeted LLN platform that incorporated a CD47-derived self-peptide (SP) to reduce macrophage phagocytosis and a mannose ligand to enhance DC uptake. Our results showed that the synergistic dual modification of these LLNs with SP and mannose (SM-LLNs) substantially increased mRNA expression in lymph nodes (LNs). Additionally, SM-LLNs promoted DC maturation, enhanced antigen-specific T cell production, and elicited potent and sustained antiviral immune responses. These findings underscore the critical role of ligand modification in mRNA vaccine design and highlight our dual-modified LLN platform as a promising approach for enhancing mRNA-based vaccinations.