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嵌合四跨膜蛋白-亮氨酸氨肽酶亚单位疫苗对仓鼠华支睾吸虫感染的部分保护作用。

Partial protection with a chimeric tetraspanin-leucine aminopeptidase subunit vaccine against Opisthorchis viverrini infection in hamsters.

机构信息

Department of Parasitology, Faculty of Medicine, Khon Kaen University, Thailand; Hai Duong Medical Technical University, Hai Duong city, Hai Duong province, Viet Nam.

Department of Parasitology, Faculty of Medicine, Khon Kaen University, Thailand.

出版信息

Acta Trop. 2020 Apr;204:105355. doi: 10.1016/j.actatropica.2020.105355. Epub 2020 Jan 25.

Abstract

Opisthorchiasis is a serious public health problem in East Asia and Europe. The pathology involves hepatobiliary abnormalities such as cholangitis, choledocholithiasis and tissue fibrosis that can develop into cholangiocarcinoma. Prevention of infection is difficult as multiple social and behavioral factors are involved, thus, progress on a prophylactic vaccine against opisthorchiasis is urgently needed. Opisthorchis viverrini tetraspanin-2 (Ov-TSP-2) was previously described as a potential vaccine candidate conferring partial protection against O. viverrini infections in hamsters. In this study, we generated a recombinant chimeric form of the large extracellular loop of Ov-TSP-2 and O. viverrini leucine aminopeptidase, designated rOv-TSP-2-LAP. Hamsters were vaccinated with 100 and 200 µg of rOv-TSP-2-LAP formulated with alum-CpG adjuvant via intraperitoneal injection and evaluated the level of protection against O. viverrini infection. Our results demonstrated that the number of worms recovered from hamsters vaccinated with either 100 or 200 µg of rOv-TSP-2-LAP were significantly reduced by 27% compared to the adjuvant control group. Furthermore, the average length of worms recovered from animals vaccinated with 200 μg of rOv-TSP-2-LAP was significantly shorter than those from the control adjuvant group. Immunized hamsters showed significantly increased serum levels of anti-rOv-TSP-2 IgG and IgG1 compared to adjuvant control group, suggesting that rOv-TSP-2-LAP vaccination induces a mixed Th1/Th2 immune response in hamsters. Therefore, the development of a suitable vaccine against opisthorchiasis requires further work involving new vaccine technologies to improve immunogenicity and protective efficacy.

摘要

华支睾吸虫病是东亚和欧洲的一个严重公共卫生问题。其病理学涉及肝胆异常,如胆管炎、胆总管结石和组织纤维化,这些都可能发展为胆管癌。由于涉及多种社会和行为因素,感染的预防很困难,因此,迫切需要开发针对华支睾吸虫病的预防性疫苗。华支睾吸虫四跨膜蛋白-2(Ov-TSP-2)先前被描述为一种有希望的候选疫苗,可在仓鼠中对华支睾吸虫感染提供部分保护。在这项研究中,我们生成了华支睾吸虫亮氨酸氨肽酶的大细胞外环的重组嵌合形式,命名为 rOv-TSP-2-LAP。通过腹腔内注射,用明矾-CpG 佐剂对仓鼠进行了 100 和 200μg rOv-TSP-2-LAP 的疫苗接种,并评估了针对华支睾吸虫感染的保护水平。结果表明,与佐剂对照组相比,接种 100 或 200μg rOv-TSP-2-LAP 的仓鼠体内回收的蠕虫数量分别显著减少了 27%。此外,接种 200μg rOv-TSP-2-LAP 的动物体内回收的蠕虫平均长度明显短于佐剂对照组。与佐剂对照组相比,免疫仓鼠的血清抗-rOv-TSP-2 IgG 和 IgG1 水平显著升高,表明 rOv-TSP-2-LAP 疫苗接种可诱导仓鼠产生混合 Th1/Th2 免疫反应。因此,开发针对华支睾吸虫病的合适疫苗需要进一步的工作,涉及新的疫苗技术,以提高免疫原性和保护效力。

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