A newly characterized malaria antigen on erythrocyte and merozoite surfaces induces parasite inhibitory antibodies

Ian C. Michelow, Sangshin Park, Shu Whei Tsai, Bonnie Rayta, Charisse Flerida A. Pasaje, Sara Nelson, Angela M. Early, Anne P. Frosch, George Ayodo, Dipak K. Raj, Christina E. Nixon, Christian P. Nixon, Sunthorn Pond-Tor, Jennifer F. Friedman, Michal Fried, Patrick E. Duffy, Karine G. Le Roch, Jacquin C. Niles, Jonathan D. Kurtis

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere20200170
JournalJournal of Experimental Medicine
Volume218
Issue number9
DOIs
StatePublished - 3 Aug 2021

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