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

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.

doi:10.1084/jem.20200170

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

Journal Article · Tue Aug 03 00:00:00 EDT 2021 · Journal of Experimental Medicine

DOI:https://doi.org/10.1084/jem.20200170· OSTI ID:1811939

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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.

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Research Organization:: Brown Univ., Providence, RI (United States)

Sponsoring Organization:: Bill and Melinda Gates Foundation; National Institutes of Health (NIH); National Science Foundation (NSF); USDOE

OSTI ID:: 1811939

Alternate ID(s):: OSTI ID: 1816668

Journal Information:: Journal of Experimental Medicine, Journal Name: Journal of Experimental Medicine Journal Issue: 9 Vol. 218; ISSN 0022-1007

Publisher:: Rockefeller University PressCopyright Statement

Country of Publication:: United States

Language:: English

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