Year-end Sale % OFF 
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.
Highlights
The human malaria parasite, Plasmodium falciparum (Pf), claims >400,000 lives each year despite decades of intensive public health interventions in endemic areas (WHO, 2020)
Using dual IF labeling against Pf erythrocyte membrane and merozoite antigen 1 (PfEMMA1) and ring-exported protein-1 (REX1; Fig. 3 A) or skeleton-binding protein 1 (SBP1; Fig. 3 B), both structural components of Maurer’s clefts (MC), we showed colocalization of these proteins in the punctate structures, whereas no proteins were labeled with preimmune sera (Fig. 3 C)
We showed that PfEMMA1 is closely associated with glycophorin A (GPA) detected using an anti-GPA antibody that recognizes an intracellular GPA epitope (Fig. 3 D)
Summary
The human malaria parasite, Plasmodium falciparum (Pf), claims >400,000 lives each year despite decades of intensive public health interventions in endemic areas (WHO, 2020). Global efforts to combat malaria have met with rapidly emerging resistance to frontline antimalarial agents and insecticides (Hemingway et al, 2016). RTS,S, the most advanced malaria vaccine candidate, had limited efficacy and durability in phase III trials (Olotu et al, 2016). At least 50 predominantly subunit malaria vaccines as well as whole sporozoite vaccines are currently under investigation in preclinical or clinical trials (WHO, 2017). The subunit candidates are derived from
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
