A newly characterized malaria antigen on erythrocyte and merozoite surfaces induces parasite inhibitory antibodies
Name
jem_20200170.pdf
Description
Published version
Size
5.51 MB
Format
Adobe PDF
Checksum (MD5)
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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
Date Issued
September 6, 2021
Journal
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1084/jem.20200170
