Title :

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.

Authors :

Musasia FK, Nkumama IN, Frank R, Kipkemboi V, Schneider M, Mwai K, Odera DO, Rosenkranz M, Fürle K, Kimani D, Tuju J, Njuguna P, Hamaluba M, Kapulu MC, Wardemann H; CHMI-SIKA Study Team, Osier FHA

PubMed link :

Journals :

Nat Commun. 2022