Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
Division of Infectious Diseases, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Science. 2014 May 23;344(6186):871-7. doi: 10.1126/science.1254417.
Novel vaccines are urgently needed to reduce the burden of severe malaria. Using a differential whole-proteome screening method, we identified Plasmodium falciparum schizont egress antigen-1 (PfSEA-1), a 244-kilodalton parasite antigen expressed in schizont-infected red blood cells (RBCs). Antibodies to PfSEA-1 decreased parasite replication by arresting schizont rupture, and conditional disruption of PfSEA-1 resulted in a profound parasite replication defect. Vaccination of mice with recombinant Plasmodium berghei PbSEA-1 significantly reduced parasitemia and delayed mortality after lethal challenge with the Plasmodium berghei strain ANKA. Tanzanian children with antibodies to recombinant PfSEA-1A (rPfSEA-1A) did not experience severe malaria, and Kenyan adolescents and adults with antibodies to rPfSEA-1A had significantly lower parasite densities than individuals without these antibodies. By blocking schizont egress, PfSEA-1 may synergize with other vaccines targeting hepatocyte and RBC invasion.
新型疫苗的研发迫在眉睫，以减轻严重疟疾的负担。我们采用差异全蛋白筛选方法，鉴定出恶性疟原虫裂殖子外排抗原-1（PfSEA-1），这是一种在裂殖子感染的红细胞（RBC）中表达的 244 千道尔顿寄生虫抗原。针对 PfSEA-1 的抗体通过阻止裂殖子破裂来抑制寄生虫的复制，而 PfSEA-1 的条件性破坏导致严重的寄生虫复制缺陷。用重组疟原虫伯氏疟原虫 PbSEA-1 对小鼠进行疫苗接种可显著降低寄生虫血症，并在致死性伯氏疟原虫 ANKA 株感染后延迟死亡。坦桑尼亚儿童体内存在针对重组 PfSEA-1A（rPfSEA-1A）的抗体时，不会发生严重疟疾，肯尼亚青少年和成年人体内存在针对 rPfSEA-1A 的抗体时，寄生虫密度明显低于没有这些抗体的个体。通过阻断裂殖子外排，PfSEA-1 可能与其他针对肝细胞和 RBC 入侵的疫苗产生协同作用。
