PV-10 enhances immune responses in hepatitis B vaccination through STING pathway.

Despite the efficacy of current hepatitis B vaccines, approximately 10% of immunocompetent individuals remain non-responsive, underscoring the urgent need for novel adjuvants to enhance vaccine-induced immunity. In this study, we investigated PV-10, a 10% Rose Bengal solution, for its potential to activate the stimulator of interferon genes (STING) pathway and enhance both innate and adaptive immune responses. Through molecular docking, we demonstrated that Rose Bengal binds to the ligand-binding domain of STING with an affinity of -7.1 kcal/mol (-7.0 to -9.0 kcal/mol for moderate binding), promoting dimer stabilization via hydrophobic and hydrogen-bonding interactions. In the human acute monocytic leukemia cell line THP-1, treatment with PV-10 induced the phosphorylation of key downstream signaling proteins, including TBK1, IRF3, and NF-κB p65, and uniquely generated a high molecular weight STING band indicative of dimer formation. Cytokine profiling revealed a time-dependent increase in pro-inflammatory cytokines and chemokines following PV-10 treatment. Furthermore, in an in vitro model, dendritic cells were pulsed with hepatitis B surface antigen (HBsAg)-derived peptides, HBV-1 (TVELLSFLPSDFFPSV, extended HBsAg epitope) and HBV-2 (FLPSDFFPSV, minimal cytotoxic T lymphocyte epitope) and then the pulsed DCs were used to prime CD8+ T-cells. HBsAg-primed CD8+ T-cells exhibited significantly enhanced IFN-γ secretion when co-cultured with HBsAg-positive hepatoma cells in the presence of PV-10 compared to vehicle-treated controls. These findings indicate that PV-10 functions as a potent STING agonist, stabilizing STING dimerization, and eliciting an immune microenvironment conducive to robust antigen presentation and T-cell activation, thereby demonstrating its potential as a novel adjuvant for improving hepatitis B vaccine efficacy, particularly in vaccine non-responders.