Basic study for the recombinant SERA malaria vaccine development

我们利用恶性疟原虫丝氨酸重复抗原（SERA 5）的N端结构域SE 36重组蛋白研制了一种有效的疟疾疫苗。已进行了横断面田间研究以评估SE 36蛋白的天然获得性免疫在疟疾保护中的贡献，并显示抗SE 36 IgG 3滴度与症状和血寄生虫血症两者之间存在强负相关性。此外，我们发现，在队列中，针对SE 36的血清转换率在成人中为50%或更低，在年轻一代中低于10%。这些结果表明SERA的N-末端结构域是一个隐藏的保护性抗原，就像疟原虫的阿基里斯之踵一样，在GMP条件下制备的临床级BK-SE 36，即纯化的SE 36蛋白吸附在氢氧化铝凝胶上，在黑猩猩中是安全的，并且具有高度的免疫原性。此外，该产品在恶性疟原虫攻击感染后对松鼠猴提供了显著的保护。免疫猴的抗体滴度通过攻击感染而增强。BK-SE 36的安全性和免疫原性在日本的I期临床试验中得到证实。

We have been developing an effective malaria vaccine by using a recombinant SE36 protein, N-terminal domain of Serine Repeat Antigen (SERA5) of Plasmodium falcaprum. Cross sectional field studies have been conducted to evaluate the contribution of naturally acquired immunity of SE36 protein in malaria protection and shown that a strong negative correlations between anti-SE36 IgG3 titer and both of the symptoms and blood parasitemia. In addition, we found that sero-conversion rates against SE36 were 50% or less in adults and less than 10% in younger generations in the cohorts. These findings strongly suggest that N-terminal domain of SERA is a hidden protective antigen like as Achilles heel of malaria parasite.The clinical grade BK-SE36, the purified SE36 protein adsorbed to aluminum hydroxide gel, prepared under GMP conditions was safe and highly immunogenic in Chimpanzees. In addition, the product provided significant protection in Squirrel monkeys after P falciparum challenge infection. The antibody titers in immunized monkeys were boosted by the challenge infection. Safety and Immunogenicity of BK-SE36 were confirmed in Phase I clinical trial in Japan.