Primary Evaluation of Immune Responses in Mice After Immunization With Ferritin Nanoparticle‐Displayed Taenia solium TSOL18

ABSTRACT Cysticercosis, caused by the larval stage of Taenia solium , remains a major neglected tropical disease with limited vaccine options. Although the oncospheral antigen TSOL18 confers efficient protection, its immunogenicity and durability remain suboptimal. Here, we engineered a ferritin‐based nanoparticle vaccine platform to improve TSOL18 antigen features, presentation efficiency and immune activation. The mature TSOL18 protein (lacking the N‐terminal signal peptide) was genetically fused to Helicobacter pylori ferritin either alone (TF) or together with a multiepitope peptide (GK1, KETc1, KETc12) and CD40 (TMCF), generating self‐assembling nanoparticles of approximately 15 nm in diameter, as confirmed by transmission electron microscopy, dynamic light scattering and immunogold labeling. All formulations exhibited endotoxin levels below the United States Pharmacopeia‐recommended limit (5 EU/kg), and safety assessment in mice revealed no significant alterations in serum alanine aminotransferase, aspartate aminotransferase, or ferritin levels, indicating a favorable safety profile. Compared with soluble TSOL18, the stability of nanoantigens was significantly improved, and both nanoparticle formulations (administered at equimolar doses with 20 μg soluble TSOL18) elicited significantly higher and more sustained TSOL18‐specific antibody responses than the non‐nanoparticle antigen, accompanied by enhanced CD4 + T cell activation and a Th2‐skewed cytokine profile characterized by elevated interleukin‐4 (IL‐4) production in BALB/c mice. Notably, incorporation of immunostimulatory epitopes further augmented cellular immune responses. Collectively, these findings demonstrate that ferritin‐mediated nanoparticle display substantially improves the magnitude and quality of TSOL18‐induced immunity while maintaining a favorable safety profile, providing a scalable strategy to overcome key limitations of current cysticercosis subunit vaccines.