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

• DOI: 10.1084/jem.20200170
• Publication Date: 2021-08-03T14:07:06Z
• Authors: Ian C. Michelow; Sangshin Park; Shu-Whei Tsai; Bonnie Rayta; Charisse Flerida ...; 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
• Keywords: Plasmodium berghei; Merozoite surface protein

We previously identified a Plasmodium falciparum (Pf) protein of unknown function encoded by single-copy gene, PF3D7_1134300, as target antibodies in plasma Tanzanian children whole-proteome differential screen. Here we characterize this blood-stage antigen that localizes to the surface membranes both parasitized erythrocytes and merozoites, hence its designation Pf erythrocyte membrane merozoite 1 (PfEMMA1). Mouse anti-PfEMMA1 antisera affinity-purified human inhibited growth P. strains up 68% inhibition assays. Following challenge with uniformly fatal berghei (Pb) ANKA, 40% mice immunized recombinant PbEMMA1 self-cured, median survival lethally infected was 2.6-fold longer than controls (21 vs. 8 d, P = 0.005). Furthermore, high levels naturally acquired were associated 46% decrease parasitemia over 2.5 yr follow-up children. Together, these findings suggest PfEMMA1 mediate protection against malaria.