Cage-Assembled Antigenic Particle Vaccine (CAP-V) Orchestrates Balanced Th1/Th2 Immunity and Potent Protection Against Alveolar Echinococcosis

Alveolar echinococcosis (AE) is a life-threatening zoonotic disease caused by the larval stage of Echinococcus multilocularis ( E. multilocularis ). It is characterized by the tumor-like invasive growth pattern and limited treatment options. Although immunoprophylaxis represents a promising strategy, it is difficult to achieve sufficient immune activation without disrupting Th1/Th2 immune homeostasis. Here we report a cage-assembled antigenic particle vaccine (CAP-V) that leverages a self-assembling protein nanocage to elicit protective and immunologically balanced anti-parasitic immunity. CAP-V is constructed using an engineered circularly permuted E2 (CPE2) scaffold to display the full-length E. multilocularis 14-3-3 antigen through either genetic fusion or post-assembly SpyCatcher–SpyTag conjugation. Both vaccine sequences formulations assemble into homogeneous nanoparticles and can be efficiently produced in Escherichia coli . Mechanistically, Em14-3-3 CAP-V enhanced antigen uptake and dendritic cell maturation, thereby promoting antigen presentation and triggering a coordinated immune response. In vivo immunization induces concurrent Th1- and Th2-associated cytokine responses without dominant immune polarization. Importantly, this balanced immune profile is associated with significant protection against E. multilocularis challenge, reflected by reduced parasite burden and ameliorated tissue pathology. Together, these findings demonstrate Em14-3-3 CAP-V as a modular and mechanistically informed protein nano-vaccine platform and highlight its potential for immunoprophylaxis against AE and other chronic helminthic diseases.