Key Laboratory of Animal Parasitology, Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, China.
College of Animal Science, Henan Institute of Science and Technology, Xinxiang, Henan Province, 453003, China.
Parasit Vectors. 2017 Jun 9;10(1):288. doi: 10.1186/s13071-017-2229-y.
Schistosomiasis remains an important global public health problem, as millions of people are at risk of acquiring infection. An ideal method for sustainable control of schistosomiasis would be to develop an efficient vaccine. Schistosomes can survive in the host vascular system by immune evasion, regulating the host complement cascade. Schistosoma japonicum tetraspanning orphan receptor (SjTOR) is a complement regulator, which is a tegument membrane protein. To date there is no experimental evidence to explain the function of SjTOR.
We cloned the first extracellular domain of the SjTOR (SjTOR-ed1) gene and expressed the gene in Escherichia coli. The expression level of SjTOR in different developmental stages of S. japonicum was assessed by quantitative real-time RT-PCR. Western blotting showed that recombinant SjTOR-ed1 (rSjTOR-ed1) could be recognised by schistosome-infected mouse serum. Immunolocalization indicated that the protein was mainly distributed on the tegument of the parasite. Haemolytic assays and ELISA revealed that rSjTOR-ed1 could inhibit complement hemolysis and bind to complement C2. Purified rSjTOR-ed1 emulsified with ISA206 adjuvant could induce a significant reduction of worm burden from 24.51 to 26.51%, and liver egg numbers from 32.92 to 39.62% in two independent trials in mice.
The results of this study indicated that rSjTOR-ed1 could inhibit complement hemolysis and bind to complement C2, and it is a potential vaccine candidate that protects against S. japonicum infection.
血吸虫病仍然是一个重要的全球公共卫生问题,因为数以百万计的人面临感染的风险。可持续控制血吸虫病的理想方法是开发有效的疫苗。血吸虫可以通过免疫逃避在宿主血管系统中生存,调节宿主补体级联。日本血吸虫四跨膜孤儿受体(SjTOR)是一种补体调节剂,是一种表皮膜蛋白。迄今为止,没有实验证据可以解释 SjTOR 的功能。
我们克隆了 SjTOR 的第一个细胞外结构域基因(SjTOR-ed1),并在大肠杆菌中表达了该基因。通过定量实时 RT-PCR 评估 SjTOR 在日本血吸虫不同发育阶段的表达水平。Western blot 显示重组 SjTOR-ed1(rSjTOR-ed1)可被感染血吸虫的小鼠血清识别。免疫定位表明该蛋白主要分布在寄生虫的表皮上。溶血试验和 ELISA 表明 rSjTOR-ed1 可抑制补体溶血并与补体 C2 结合。用 ISA206 佐剂乳化的纯化 rSjTOR-ed1 可在两项独立的小鼠试验中分别将虫体负荷从 24.51%降低到 26.51%,肝卵数从 32.92%降低到 39.62%。
本研究结果表明,rSjTOR-ed1 可抑制补体溶血并与补体 C2 结合,是一种有潜力的疫苗候选物,可预防日本血吸虫感染。