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.
Progress toward an effective malaria vaccine
The history of efforts to develop a malaria vaccine has been long and difficult. Raj et al. probed for molecules produced by this blood parasite that are recognized by natural immune responses of people living in malaria-endemic areas of Africa. One, PfSEA-1, blocked parasite exit from red blood cells. Vaccination experiments with mouse malaria showed almost fourfold reduction in parasitemia; moreover, passive transfer of PfSEA-1 antibodies transferred protection from mouse to mouse. Encouragingly, the presence of PfSEA-1 antibodies correlates with significant protection from severe malaria in children and adolescents from Kenya and Tanzania.