Phagocytosis of Plasmodium falciparum ring-stage parasites predicts protection against malaria

Nat Commun. 2022 Jul 14;13(1):4098. doi: 10.1038/s41467-022-31640-6.

Abstract

Ring-infected erythrocytes are the predominant asexual stage in the peripheral circulation but are rarely investigated in the context of acquired immunity against Plasmodium falciparum malaria. Here we compare antibody-dependent phagocytosis of ring-infected parasite cultures in samples from a controlled human malaria infection (CHMI) study (NCT02739763). Protected volunteers did not develop clinical symptoms, maintained parasitaemia below a predefined threshold of 500 parasites/μl and were not treated until the end of the study. Antibody-dependent phagocytosis of both ring-infected and uninfected erythrocytes from parasite cultures was strongly correlated with protection. A surface proteomic analysis revealed the presence of merozoite proteins including erythrocyte binding antigen-175 and -140 on ring-infected and uninfected erythrocytes, providing an additional antibody-mediated protective mechanism for their activity beyond invasion-inhibition. Competition phagocytosis assays support the hypothesis that merozoite antigens are the key mediators of this functional activity. Targeting ring-stage parasites may contribute to the control of parasitaemia and prevention of clinical malaria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Erythrocytes / parasitology
  • Humans
  • Malaria*
  • Malaria, Falciparum* / parasitology
  • Merozoites
  • Parasitemia
  • Parasites*
  • Phagocytosis
  • Plasmodium falciparum
  • Proteomics

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan

Associated data

  • ClinicalTrials.gov/NCT02739763