Field evaluation of vaccine candidates against schistosomiasis japonica and molecular analysis of vaccine efficacy

日本血吸虫病候选疫苗现场评价及疫苗功效分子分析

基本信息

批准号：
12576009
负责人：
OHTA Nobuo
金额：
$ 9.73万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

In the year of 2002, we prepared a large amount of recombinant protein of calpain of Schistosoma japonicum, and by the use of the recombinant protein, we produced monoclonal antibodies to S.japonicum calpain and also tested their vaccine effects in pigs. Immunohistochemistry using our mAbs revealed tissue distribution and changes of expression in developmental stages in S.japonicum. We observed strong signal in the excretory grand of cercariae. This seemed to explain a probable explanation of vaccine efficacy of calpain. In our pig trials, we observed significant reduction in egg production, however, no reduction in worm burden occurred. Durning experimental infection in pigs, there was no booster effect for antibody production to calpain, and this might explain not so good effects as were observed for paramyosin in pig trials. DNA vaccination was also investigated. As a rout of DNA inoculation, intradermal injection at ear pad induced strong antibody production. In our previous results, Th1-dominant responses seem to be important for vaccine effects. In line with this, we tested effects of CpG oligonucleotides in protective immunity to S.japonicum. Mice treated with CpG induced strong Th1 responses and significant reduction in egg granuloma formation in the liver. Intranasal treatment of CpG also induced strong effects comparable to those by intramuscular injection. Considering short half-life of CpG in vivo, repeated treatment is needed. Our intranasal treatment as a non-invasive inoculation is good for repeated treatment of CpG. As a cooperative research with Chinese counterparts, we made progress of calpain vaccine for schistosomiasis japonica, and the near future prospect has been fixed in our research project.

在2002年，我们准备了大量的Japonicum钙蛋白酶钙蛋白酶的重组蛋白，并通过使用重组蛋白，生产了针对乳链球菌链球菌的单克隆抗体，并在猪中测试了它们的疫苗作用。使用我们的mAB的免疫组织化学揭示了japonicum中发育阶段的组织分布和表达变化。我们观察到Cercariae排泄物中的强信号。这似乎解释了钙蛋白酶疫苗功效的可能解释。在我们的猪试验中，我们观察到卵产量的显着减少，但是，蠕虫负担没有减轻。在猪中刺入实验感染，抗体产生钙蛋白酶没有促进作用，这可能解释了猪试验中帕莫西素的好作用。还研究了DNA疫苗接种。作为DNA接种的溃败，耳垫处的皮内注射会诱导较强的抗体产生。在我们先前的结果中，Th1主导反应对于疫苗作用似乎很重要。与此一致，我们测试了CpG寡核苷酸对japonicum的保护性免疫的影响。用CPG处理的小鼠诱导了强烈的Th1反应，并在肝脏中卵肉芽肿的形成显着降低。 CpG的鼻内治疗还引起了与肌内注射相当的强大作用。考虑到体内CpG的半衰期短，需要重复治疗。我们作为无创接种的鼻内治疗非常适合重复治疗CPG。作为与中国同行的合作研究，我们在japonica的血吸虫病中取得了进展，而我们的研究项目已经确定了不久的将来的前景。