Immunogen-sponge hydrogel reverses TIM-3-mediated dendritic cell dysfunction in alveolar echinococcosis

Alveolar echinococcosis (AE) is a serious parasitic disease with limited treatments and no approved vaccine. Here, we identify TIM-3-associated dendritic cell (DC) dysfunction as a key barrier to protective immunity in AE, marked by impaired antigen presentation after chronic exposure to cyst-fluid-derived immunosuppressive antigens. To overcome this barrier, we develop a SHIFT-engineered immunogen-sponge hydrogel based on Pluronic F127. This biomimetic platform recruits DCs while physically blocking their interaction with suppressive parasite antigens, thereby reducing TIM-3 expression, and provides sustained release of protoscolex-derived T and B cell epitope peptides. In prophylactic and therapeutic AE mouse models, the immunogen-sponge restores DC function, enhances adaptive immunity, and markedly reduces parasite burden and hepatic dissemination. Combination with albendazole further improves parasite clearance. Together, these findings establish a translatable hydrogel vaccine strategy for reversing DC dysfunction in AE and other chronic immunosuppressive infections.