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

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.

INSTRUMENT(S):

ORGANISM(S): Plasmodium Falciparum (isolate 3d7)

DISEASE(S): Plasmodium Falciparum Malaria

SUBMITTER: James Tuju  

LAB HEAD: Prof Faith Osier

PROVIDER: PXD033964 | Pride | 2022-08-11

REPOSITORIES: Pride