Peptides Derived of Kunitz-Type Serine Protease Inhibitor as Potential Vaccine Against Experimental Schistosomiasis
Peptides Derived of Kunitz-Type Serine Protease Inhibitor as Potential Vaccine Against Experimental Schistosomiasis
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DOI：
10.3389/fimmu.2019.02498
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发表时间：
2019-11-01
影响因子：
7.3
通讯作者：
Muro, Antonio
中科院分区：
文献类型：
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作者：
Hernandez-Goenaga, Juan;Lopez-Aban, Julio;Muro, Antonio
血吸虫病是撒哈拉以南非洲、中国、东南亚以及南美洲和中美洲地区的一个重大公共卫生问题，影响约1.89亿人。Kunitz型丝氨酸蛋白酶抑制剂已被确定为其他扁形虫寄生虫与其哺乳动物宿主相互作用的重要参与者。它们参与宿主血液凝固、纤维蛋白溶解、炎症和离子通道阻断，所有这些都是关键的生物学过程，这使它们成为开发疫苗的有趣靶点。在这里，我们评估化学合成的T-和B-细胞肽表位来自曼氏血吸虫kunitz蛋白的保护效力。在S. mansoni的基因组，并通过RNA-seq分析它们的表达。基因表达分析显示，kunitz蛋白Smp_147730（Syn. Smp_311670）与入侵尾蚴相比，在童虫和蠕虫中显著上调。使用生物信息学工具预测T细胞和B细胞表位，化学合成，并在佐剂适应（ADAD）疫苗接种系统中配制。BALB/c小鼠接种S.曼氏尾蚴。Kunitz肽在接种的BALB/c小鼠中具有高度保护性，显示成年雌性小鼠的恢复率（89-91%）以及小鼠肝脏（77-81%）和肠道（57-77%）中捕获的卵数量显著降低。此外，与感染的对照小鼠相比，接种疫苗的小鼠的肝脏病变显著减少（64-65%）。疫苗接种方案对两种肽均耐受良好。我们建议单独或联合使用这些肽作为抗血吸虫病疫苗的可靠候选物。
Schistosomiasis is a significant public health problem in sub-Saharan Africa, China, Southeast Asia, and regions of South and Central America affecting about 189 million people. Kunitz-type serine protease inhibitors have been identified as important players in the interaction of other flatworm parasites with their mammalian hosts. They are involved in host blood coagulation, fibrinolysis, inflammation, and ion channel blocking, all of them critical biological processes, which make them interesting targets to develop a vaccine. Here, we evaluate the protective efficacy of chemically synthesized T- and B-cell peptide epitopes derived from a kunitz protein from Schistosoma mansoni. Putative kunitz-type protease inhibitor proteins were identified in the S. mansoni genome, and their expression was analyzed by RNA-seq. Gene expression analyses showed that the kunitz protein Smp_147730 (Syn. Smp_311670) was dramatically and significantly up-regulated in schistosomula and adult worms when compared to the invading cercariae. T- and B-cell epitopes were predicted using bioinformatics tools, chemically synthesized, and formulated in the Adjuvant Adaptation (ADAD) vaccination system. BALB/c mice were vaccinated and challenged with S. mansoni cercariae. Kunitz peptides were highly protective in vaccinated BALB/c mice showing significant reductions in recovery of adult females (89-91%) and in the numbers of eggs trapped in the livers (77-81%) and guts (57-77%) of mice. Moreover, liver lesions were significantly reduced in vaccinated mice (64-65%) compared to infected control mice. The vaccination regime was well-tolerated with both peptides. We propose the use of these peptides, alone or in combination, as reliable candidates for vaccination against schistosomiasis.