Phumrattanaprapin Wuttipong, Shalash Ahmed O, Skwarczynski Mariusz, Smout Michael J, Laha Thewarach, Toth Istvan, Loukas Alex
Princess Srisavangavadhana Faculty of Medicine, Chulabhorn Royal Academy, Bangkok 10210, Thailand.
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia.
Vaccine. 2025 Jun 17;61:127400. doi: 10.1016/j.vaccine.2025.127400.
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.
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.
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.
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.
在东南亚，华支睾吸虫慢性感染是胆管癌的主要促成因素，因此需要开发有效的疫苗。本研究旨在评估在仓鼠模型中针对华支睾吸虫的基于肽的口服疫苗的免疫原性和保护效果。
合成了候选疫苗抗原Ov-TSP-2的五个蛋白片段，其中LEL4和SEL肽被确定为免疫原性最强的。这些肽与聚丙烯酸甲酯（PMA）偶联用于纳米颗粒自组装和黏膜免疫。仓鼠接受四次口服免疫，并用华支睾吸虫尾蚴进行攻击，以评估免疫反应和保护作用。
接受LEL4免疫的仓鼠表现出抗原特异性血清IgG、黏膜IgG和IgA滴度升高。这种免疫反应与虫卵计数和虫负荷显著降低相关。从接种疫苗的仓鼠体内回收的虫体生长发育迟缓，表明寄生虫发育受损。
本研究证实了LEL4作为一种针对华支睾吸虫的基于肽的口服疫苗的潜力。通过诱导黏膜和全身免疫，该疫苗为对抗华支睾吸虫病及其相关癌症风险提供了一种有前景的策略，标志着肝吸虫控制方面的重大进展。
