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Raj, Dipak K; Das Mohapatra, Alok; Jnawali, Anup; Zuromski, Jenna; Jha, Ambrish; Cham-Kpu, Gerald; Sherman, Brett; Rudlaff, Rachel M; Nixon, Christina E; Hilton, Nicholas; Oleinikov, Andrew V; Chesnokov, Olga; Merritt, Jordan; Pond-Tor, Sunthorn; Burns, Lauren; Jolly, Grant; Ben Mamoun, Choukri; Kabyemela, Edward; Muehlenbachs, Atis; Lambert, Lynn; Orr-Gonzalez, Sachy; Gnädig, Nina F; Fidock, David A; Park, Sangshin; Dvorin, Jeffrey D; Pardi, Norbert; Weissman, Drew; Mui, Barbara L; Tam, Ying K; Friedman, Jennifer F; Fried, Michal; Duffy, Patrick E; Kurtis, Jonathan D
Nature (London), 06/2020, Letnik: 582, Številka: 7810Journal Article
Malaria caused by Plasmodium falciparum remains the leading single-agent cause of mortality in children , yet the promise of an effective vaccine has not been fulfilled. Here, using our previously described differential screening method to analyse the proteome of blood-stage P. falciparum parasites , we identify P. falciparum glutamic-acid-rich protein (PfGARP) as a parasite antigen that is recognized by antibodies in the plasma of children who are relatively resistant-but not those who are susceptible-to malaria caused by P. falciparum. PfGARP is a parasite antigen of 80 kDa that is expressed on the exofacial surface of erythrocytes infected by early-to-late-trophozoite-stage parasites. We demonstrate that antibodies against PfGARP kill trophozoite-infected erythrocytes in culture by inducing programmed cell death in the parasites, and that vaccinating non-human primates with PfGARP partially protects against a challenge with P. falciparum. Furthermore, our longitudinal cohort studies showed that, compared to individuals who had naturally occurring anti-PfGARP antibodies, Tanzanian children without anti-PfGARP antibodies had a 2.5-fold-higher risk of severe malaria and Kenyan adolescents and adults without these antibodies had a twofold-higher parasite density. By killing trophozoite-infected erythrocytes, PfGARP could synergize with other vaccines that target parasite invasion of hepatocytes or the invasion of and egress from erythrocytes.
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in: SICRIS
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