Basic study for the recombinant SERA malaria vaccine development

我们一直在利用恶性疟原虫丝氨酸重复抗原N端结构域(SERA5)的重组SE36蛋白开发一种有效的疟疾疫苗。横断面现场研究评价了SE36蛋白天然获得性免疫在疟疾防治中的作用，结果表明，抗SE36 IgG3效价与疟疾症状和血液寄生虫血症均呈显著负相关。此外，我们发现，在队列中的成年人中，SE36的血清转换率为50%或更低，而在年轻一代中，这一比例不到10%。这些发现有力地表明，血清N末端结构域是一种隐藏的保护性抗原，就像疟疾原虫的阿喀琉斯脚跟一样。在GMP条件下制备的临床级BK-SE36蛋白，吸附在氢氧化铝凝胶上，对黑猩猩是安全的，具有很强的免疫原性。此外，该产品对恶性疟原虫攻击感染后的松鼠猴有明显的保护作用。攻击感染可提高免疫猕猴的抗体效价。日本的I期临床试验证实了BK-SE36的安全性和免疫原性。

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.