A newly characterized malaria antigen on erythrocyte and merozoite surfaces induces parasite inhibitory antibodies.
J Exp Med
; 218(9)2021 09 06.
Article
in En
| MEDLINE
| ID: mdl-34342640
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.
Full text:
1
Database:
MEDLINE
Main subject:
Plasmodium falciparum
/
Protozoan Proteins
/
Malaria, Falciparum
/
Erythrocyte Membrane
/
Merozoites
/
Antigens, Protozoan
Type of study:
Prognostic_studies
Limits:
Animals
/
Child, preschool
/
Female
/
Humans
/
Infant
Country/Region as subject:
Africa
Language:
En
Journal:
J Exp Med
Year:
2021
Type:
Article