Cage-assembled antigenic particle vaccine (CAP-V) orchestrates coordinated antigen-responsive immunity and protection against alveolar Echinococcosis

Alveolar echinococcosis (AE) i s 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 antiparasitic 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 sequence formulations assemble into homogeneous nanoparticles and can be efficiently produced in Escherichia coli . Mechanistically, CAP-V induced BMDC maturation-associated responses and coordinated cellular and humoral immunity. In vivo immunization elicited concurrent Th1- and Th2-associated responses, with a comparatively stronger IFN-γ/IgG2c-associated component. Importantly, this coordinated 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-Vs as a modular and mechanistically informed protein nanovaccine platform and highlight its potential for immunoprophylaxis against AE and other chronic helminthic diseases.