Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection

作者：Raj Dipak K; Nixon Christian P; Nixon Christina E; Dvorin Jeffrey D; DiPetrillo Christen G; Pond Tor Sunthorn; Wu Hai Wei; Jolly Grant; Pischel Lauren; Lu Ailin; Michelow Ian C; Cheng Ling; Conteh Solomon; McDonald Emily A; Absalon Sabrina; Holte Sarah E; Friedman Jennifer F; Fried Michal; Duffy Patrick E; Kurtis Jonathan D^*

来源：Science, 2014, 344(6186): 871-877.

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.

• 出版日期2014-5-23