Development of an efficacious oral peptide vaccine against infection with the carcinogenic liver fluke Opisthorchis viverrini

Objectives: Chronic Opisthorchis viverrini infection is a major contributor to cholangiocarcinoma in Southeast Asia, necessitating effective vaccine development. This study aimed to evaluate the immunogenicity and protective efficacy of peptide-based oral vaccines targeting O. viverrini in a hamster model. Methods: Five protein fragments from the vaccine candidate antigen Ov-TSP-2 were synthesized, with LEL4 and SEL peptides identified as the most immunogenic. These peptides were conjugated to polymethylacrylate (PMA) for nanoparticle self-assembly and mucosal immunization. Hamsters received four oral immunizations and were challenged with O. viverrini metacercariae to assess immune response and protection. Results: LEL4-immunized hamsters demonstrated elevated antigen-specific serum IgG, mucosal IgG, and IgA titers. This immune response correlated with significantly reduced egg counts and worm burdens. Recovered worms from vaccinated hamsters exhibited stunted growth, indicating impaired parasite development. Conclusions: This study establishes the potential of LEL4 as a peptide-based oral vaccine against O. viverrini. By inducing mucosal and systemic immunity, the vaccine offers a promising strategy for combating opisthorchiasis and its associated cancer risk, marking a significant advancement in liver fluke control.