Lymph Node-Targeted PLGA-EgG1Y162 Nanovaccine for Synergistic Immunity Against Echinococcus granulosus Infection.

BACKGROUND: Cystic echinococcosis (CE), a zoonosis caused by Echinococcus granulosus, severely endangers human and animal health in western pastoral China. Conventional surgery and chemotherapy suffer from high recurrence and toxic side effects, so immunization is urgently needed for CE prevention. METHODS: We constructed a PLGA nanovaccine loading EgG1Y162 antigen (PLGA-EgG1Y162) via double emulsion-solvent evaporation. Its physicochemical features, DC activation, in vivo lymph node retention, immune response, anti-infection protection and CD4⁺ T cell transcriptome were comprehensively detected. RESULTS: The nanovaccine showed uniform spherical morphology with an average particle size of 394 nm and 79% encapsulation efficiency, presenting favorable sustained-release performance and excellent biocompatibility. In vitro experiments verified that PLGA-EgG1Y162 was efficiently taken up by dendritic cells and effectively facilitated DC maturation. In vivo tracking demonstrated that the nanovaccine achieved prolonged retention within lymph nodes. Compared with the free antigen group and Freund's adjuvant-adjuvanted group, PLGA-EgG1Y162 induced significantly higher and longer-lasting antigen-specific IgG antibodies, markedly upregulated splenic IFN-γ, IL-4, IL-10 and TNF-α expression, and maintained elevated proportions of splenic CD4⁺ and CD8⁺ T cells. At 16 and 24 weeks post infection, vaccinated mice had remarkably fewer hepatic cysts, reduced liver-to-body weight ratios and lower serum transaminase levels, with relatively intact hepatic tissue architecture. Transcriptomic data illustrated that the vaccine reshaped CD4⁺ T cell transcriptional profiles, alleviated infection-triggered chronic inflammation, and suppressed aberrant activation of hepatic autophagy-related genes. CONCLUSION: PLGA-EgG1Y162 realizes lymph node-targeted sustained antigen delivery to elicit balanced long-lasting humoral and cellular immunity, producing prominent protection against E. granulosus. This work offers a promising immunoprophylactic candidate for cystic echinococcosis.