Abstract / Summary
Abstract Respiratory syncytial virus (RSV) poses a serious threat to the health of infants, young children, and the elderly. The development of RSV vaccines faces challenges such as Th2-biased immunopathology and insufficient immune persistence. The MF59 adjuvant has been safely used in influenza vaccines for 30 years. In this study, based on MF59, we constructed a novel composite nanoemulsion adjuvant, MF59@MDP, by incorporating the immunostimulator MDP. We exploited damage-associated molecular patterns (DAMPs), such as ATP and dsDNA, released upon tissue injury induced by high local concentrations of Span85 and Tween80 at the injection site, to promote antigen-presenting cell-mediated trafficking of MDP to lymph nodes, enhance pro-inflammatory cytokine release from lymph node dendritic cells (DCs), and modulate their epigenetic modifications. Through reprogramming of innate immune cells, this strategy corrected T cell immune bias and synergistically enhanced both humoral and cellular immunity. Furthermore, combining MF59@MDP with CpG further augmented its trained immunity potential. Mouse challenge experiments demonstrated that the MDP-containing adjuvant group more readily induced cytotoxic T lymphocyte (CTL) responses and effectively protected against viral challenge. This thesis aims to construct a novel MF59-based composite nanoemulsion adjuvant to promote the generation, persistence, and immune memory formation of RSV preF antigen-specific humoral and cellular immunity, thereby laying a foundation for the development of novel recombinant RSV vaccines.