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

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine Pub Date : 2025-06-17 DOI:10.1016/j.vaccine.2025.127400

Wuttipong Phumrattanaprapin , Ahmed O. Shalash , Mariusz Skwarczynski , Michael J. Smout , Thewarach Laha , Istvan Toth , Alex Loukas

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引用次数: 0

Abstract

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.

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一种抗肝癌吸虫感染的有效口服肽疫苗的研制

目的在东南亚地区，慢性猪瘟弧菌感染是导致胆管癌的主要原因，因此有必要开发有效的疫苗。本研究目的是在仓鼠模型上评价基于肽的口服疫苗的免疫原性和保护效果。方法从疫苗候选抗原Ov-TSP-2中合成5个蛋白片段，其中LEL4和SEL肽段免疫原性最强。这些肽被偶联到聚甲基丙烯酸酯（PMA）上，用于纳米颗粒的自组装和粘膜免疫。对仓鼠进行四次口服免疫接种，并对其进行猪弧菌囊蚴攻击，以评估免疫反应和保护作用。结果经slel4免疫的仓鼠血清抗原特异性IgG、黏膜IgG和IgA滴度升高。这种免疫反应与显著减少的卵数和蠕虫负荷相关。从接种疫苗的仓鼠身上恢复的蠕虫表现出生长迟缓，表明寄生虫发育受损。结论本研究确定了LEL4作为一种肽类口服疫苗的潜力。通过诱导粘膜和全身免疫，该疫苗为对抗蛇胸片病及其相关的癌症风险提供了一个有希望的策略，标志着肝吸虫控制的重大进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Vaccine 医学-免疫学

CiteScore

8.70

自引率

5.50%

发文量

992

审稿时长

131 days

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