Liposome-mediated simvastatin in vaccine adjuvants: Its application and mechanism

To mitigate the APC cytotoxicity associated with simvastatin (a promising adjuvant candidate), we encapsulated this drug in liposomes to generate LIPO-SIM, and explored the potential and mechanism. Formulated via ethanol injection and rotary evaporation, liposome-SIM was characterized for appearance, ζ-average, PDI, zeta potential, and encapsulation efficiency. C57BL/6 J mice were immunized with LIPO-SIM + OVA (0/21-day schedule), euthanized on day 28 to evaluate immunogenicity, safety, and antigen presentation mechanisms. In vitro, DC2.4 cells stimulated with liposome-SIM underwent RNA-Seq, metabolomics, and western blotting to clarify adjuvant mechanisms. Results showed liposome-SIM significantly increased anti-OVA IgG titers and cellular immunity, activated local lymph node macrophages/dendritic cells, and enhanced MHC-I presentation. In vitro, AMPK inhibition and NF-κB activation were observed. No organ toxicity or inflammatory storms were detected. Liposome-SIM enhances cellular immunity via the MHC-I pathway, with AMPK/NF-κB signaling as a potential key mechanism.