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Paper Chase

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

Science. May 23, 2014;344(6186):871-7.
Raj DK, Nixon CP, Nixon CE, Dvorin JD, DiPetrillo CG, Pond-Tor S, Wu HW, Jolly G, Pischel L, Lu A, Michelow IC, Cheng L, Conteh S, McDonald EA, Absalon S, Holte SE, Friedman JF, Fried M, Duffy PE, Kurtis JD.

Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA. Department of Pathology and Laboratory Medicine, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02906, USA. jonathan_kurtis@brown.edu.

Abstract:

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.