Development of Malaria Vaccine with Recombinant SERA Proteins

恶性疟原虫血清(113 KDa)是疫苗候选抗原之一，是一种大量产生的无性血期抗原，特别是在滋养体晚期和裂殖体阶段。在裂殖体破裂时，血清被加工成47 kDa、50 kDa和18 kDa的片段。我们在大肠杆菌中表达了血清蛋白的N-末端结构域(SE47‘)，结果表明重组蛋白能诱导产生寄生虫抑制性抗血清。我们通过亲和层析纯化了SE47‘-特异性IgG，以研究抗血清抗体抑制寄生虫生长的分子机制。结果如下：1)亲和纯化的抗SE47‘Ig G分子能有效抑制寄生虫的生长。2)抗SE47‘Ig G分子凝集裂殖体和裂殖子，从而抑制寄生虫的生长。3)补体固定亚类的抑制作用比其他亚类更强。4)活性补体增强了抗血清免疫球蛋白对寄生虫生长的抑制作用，裂殖体含有变性的核，表明寄生虫是通过经典的补体途径被杀死的。这些发现有力地支持了重组血清作为疟疾疫苗的可行性。

The Plasmodium falciparum SERA (113 kDa), one of the vaccine candidate antigens, is an asexual blood stage antigen produced in large amounts specifically during late trophozoite and schizonts stages. SERA is processed into 47 kDa, 50 kDa and 18 kDa fragments at the schizont rupture. We expressed N-terminal domain (SE47' ) of SERA protein in E.coli and showed that the recombinant protein induces parasite inhibitory antiserum. We purified SE47'-specific lgG by affinity chromatography to study molecular mechanisms of anti SERA anatibody to inhibit the parasite growth. The results were as follows ; 1) Affinity purified anti-SE47' IgG molecules efficiently inhibit the parasite growth. 2) Anti-SE47' IgG molecules agglutinate schizonts and merozoites, resulting in the growth inhibition of the parasite. 3) Complement-fixing subclasses lgGs are more potent in the inhibition than other subclass. 4) Active complement enhanced the parasite growth inhibition by anti SERA IgG and the resulted schizont contained degenerated nuclei, suggesting that the parasites were killed by the classical pathway of complement. These findings strongly support a feasibility of the recombinant SERA as a malaria vaccine.