Immunological enhancement of micro-nanoparticle formulated with risedronate and zinc as vaccine adjuvant in aged mice.

BACKGROUND: Elderly individuals face heightened susceptibility to infectious diseases and diminished vaccine responses. Vaccine adjuvants offer a solution. Despite aluminum adjuvant's long history, its limitations in inducing strong cellular immunity and protecting immunocompromised individuals restrict its application. Building upon our previous development of zinc salt particle-based risedronate (Zn-RS), we systematically investigated the immunoenhancing effects of Zn-RS in aged mice and thoroughly explored the underlying mechanisms responsible for these observations in this study. RESULTS: Compared to formulations using aluminum adjuvant, Zn-RS combined with either varicella-zoster virus glycoprotein E (gE) or SARS-CoV-2 monovalent STFK protein (STFK) elicited significantly higher IgG and neutralization titers, as well as superior long-term humoral immunity. Moreover, Zn-RS induced greater quantities of dendritic cells (DCs), antigen-presenting cells (APCs), follicular helper T (T(FH)) cells, Th1/Th2/Th9/Th17 type immune cells, germinal center B cells (GCBs) and plasma cells. CONCLUSIONS: These findings support Zn-RS as a promising adjuvant candidate for elderly populations, warranting further exploration of its mechanisms and potential applications.