Rescuing Dendritic Cells from Adjuvant Toxicity: Liposomal Ginsenoside Rh2 as a Dual-Action Strategy for Enhanced Vaccine Potency

Antigen-presenting cell (APC)-associated cytotoxicity is considered one of the bottlenecks restricting the development of novel vaccine adjuvants. Our present study suggested that liposome-encapsulated ginsenoside Rh2 (LP-Rh2) may effectively alleviate APC injury elicited by diverse cytotoxic immunostimulants. Combined transcriptomic and metabolomic profiling together with cellular functional assays revealed that LP-Rh2 could ameliorate mitochondrial dysfunction triggered by liposomal simvastatin (LP-SIM). Likely via elevating mitochondrial membrane potential and promoting ATP production, LP-Rh2 appears to restrain the early stage apoptosis of dendritic cells and thereby relieve statin-caused DC damage. In vivo animal observations indicated that coadministration of LP-Rh2 and LP-SIM tends to boost APC activation within draining lymph nodes. Preliminary findings demonstrated that LP-Rh2 may achieve synergistic immunostimulatory effects with LP-SIM by preserving dendritic cell (DC) homeostasis, which consequently helps strengthen both humoral and cellular immune responses. Meanwhile, no apparent toxic pathological changes were observed according to serum biochemistry and histopathological assessments of vital organs. In summary, preliminary data presumably confirmed that LP-Rh2 confers cellular protection through the regulation of mitochondrial function and apoptotic cascades, which renders it a promising candidate protective adjuvant for improving the biosafety and immune performance of cytotoxic immunostimulants.