A newly characterized malaria antigen on erythrocyte and merozoite surfaces induces parasite inhibitory antibodies
Author(s)
Michelow, Ian C; Park, Sangshin; Tsai, Shu-Whei; Rayta, Bonnie; Pasaje, Charisse Flerida A; Nelson, Sara; Early, Angela M; Frosch, Anne P; Ayodo, George; Raj, Dipak K; Nixon, Christina E; Nixon, Christian P; Pond-Tor, Sunthorn; Friedman, Jennifer F; Fried, Michal; Duffy, Patrick E; Le Roch, Karine G; Niles, Jacquin C; Kurtis, Jonathan D; ... Show more Show less
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<jats:p>We previously identified a Plasmodium falciparum (Pf) protein of unknown function encoded by a single-copy gene, PF3D7_1134300, as a target of antibodies in plasma of Tanzanian children in a whole-proteome differential screen. Here we characterize this protein as a blood-stage antigen that localizes to the surface membranes of both parasitized erythrocytes and merozoites, hence its designation as Pf erythrocyte membrane and merozoite antigen 1 (PfEMMA1). Mouse anti-PfEMMA1 antisera and affinity-purified human anti-PfEMMA1 antibodies inhibited growth of P. falciparum strains by up to 68% in growth inhibition assays. Following challenge with uniformly fatal Plasmodium berghei (Pb) ANKA, up to 40% of mice immunized with recombinant PbEMMA1 self-cured, and median survival of lethally infected mice was up to 2.6-fold longer than controls (21 vs. 8 d, P = 0.005). Furthermore, high levels of naturally acquired human anti-PfEMMA1 antibodies were associated with a 46% decrease in parasitemia over 2.5 yr of follow-up of Tanzanian children. Together, these findings suggest that antibodies to PfEMMA1 mediate protection against malaria.</jats:p>
Date issued
2021-09-06Department
Massachusetts Institute of Technology. Department of Biological EngineeringJournal
Journal of Experimental Medicine
Publisher
Rockefeller University Press