Dong Bowen, Zhong Haoran, Zhu Danlin, Wu Luobin, Wang Jinming, Li Hao, Jin Yamei
National Reference Laboratory for Animal Schistosomiasis, Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
College of Life Sciences, Shanghai Normal University, Shanghai 200234, China.
Pathogens. 2025 Jan 14;14(1):70. doi: 10.3390/pathogens14010070.
Schistosomiasis is a neglected tropical disease and the second most common parasitic disease after malaria. While praziquantel remains the primary treatment, concerns about drug resistance highlight the urgent need for new drugs and effective vaccines to achieve sustainable control. Previous proteomic studies from our group revealed that the expression of glycosyltransferase and nicastrin as proteins was higher in single-sex males than mated males, suggesting their critical roles in parasite reproduction and their potential as vaccine candidates. In this study, bioinformatic tools were employed to analyze the structural and functional properties of these proteins, including their signal peptide regions, transmembrane domains, tertiary structures, and protein interaction networks. Recombinant forms of glycosyltransferase and nicastrin were expressed and purified, followed by immunization experiments in BALB/c mice. Immunized mice exhibited significantly elevated specific IgG antibody levels after three immunizations compared to adjuvant and PBS controls. Furthermore, immunization with recombinant glycosyltransferase and nicastrin significantly reduced the reproductive capacity of female worms and liver egg burden, though egg hatchability and adult worm survival were unaffected. These findings demonstrate that recombinant glycosyltransferase and nicastrin are immunogenic and reduce female worm fecundity, supporting their potential as vaccine candidates against schistosomiasis.
血吸虫病是一种被忽视的热带疾病，是仅次于疟疾的第二常见寄生虫病。虽然吡喹酮仍然是主要治疗药物，但对耐药性的担忧凸显了迫切需要新药和有效疫苗以实现可持续控制。我们小组之前的蛋白质组学研究表明，糖基转移酶和尼卡斯特林蛋白在单性雄虫中的表达高于交配后的雄虫，表明它们在寄生虫繁殖中起关键作用及其作为疫苗候选物的潜力。在本研究中，使用生物信息学工具分析了这些蛋白质的结构和功能特性，包括它们的信号肽区域、跨膜结构域、三级结构和蛋白质相互作用网络。表达并纯化了糖基转移酶和尼卡斯特林的重组形式，随后在BALB/c小鼠中进行免疫实验。与佐剂和PBS对照组相比，免疫小鼠在三次免疫后特异性IgG抗体水平显著升高。此外，用重组糖基转移酶和尼卡斯特林免疫可显著降低雌虫的生殖能力和肝脏虫卵负荷，不过虫卵孵化率和成虫存活率未受影响。这些发现表明，重组糖基转移酶和尼卡斯特林具有免疫原性并可降低雌虫繁殖力，支持它们作为抗血吸虫病疫苗候选物的潜力。
