Development of Malaria Vaccine with Recombinant SERA Proteins

恶性疟原虫SERA（113kDa）是疫苗候选抗原之一，是特异性地在滋养体晚期和滋养体阶段大量产生的无性血液阶段抗原。SERA在鞭毛断裂处被加工成47 kDa、50 kDa和18 kDa的片段。我们在大肠杆菌中表达了SERA蛋白的N端结构域（SE47'），并证明重组蛋白可诱导抗疟原虫血清。为了研究抗SERA抗体抑制寄生虫生长的分子机制，我们用亲和层析法纯化了SE47 '特异性IgG。结果表明：1）亲和纯化的抗SE47 ' IgG分子能有效抑制寄生虫的生长。2)抗SE47 ' IgG分子凝集寄生虫和裂殖子，导致寄生虫的生长抑制。3)补体结合亚类IgG的抑制作用比其他亚类更强。4)活性补体可增强抗SERA IgG对疟原虫的生长抑制作用，产生的抗体含有退化的细胞核，提示补体是通过经典途径杀死疟原虫的。这些发现有力地支持了重组SERA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.