Musasia FK
Nkumama IN
Frank R
Kipkemboi V
Schneider M
Mwai K
Odera DO
Rosenkranz M
F├╝rle K
Kimani D
Tuju J
Njuguna P
Hamaluba M
Kapulu MC
Wardemann H
Abdi AI
Abebe Y
Bejon P
Billingsley PF
Bull PC
de Laurent Z
Hoffman SL
James ER
Kariuki S
Kimathi R
Kinyanjui S
Kivisi C
Makale J
Marsh K
Mohammed KS
Mosobo M
Musembi J
Musyoki J
Muthui M
Mwacharo J
Ndungu F
Ngoi JM
Ngoto O
Ogutu B
Olewe F
Omuoyo D
OngÔÇÖecha J
Otieno E
Shangala J
Sim BKL
Richie TL
Wambua J
Williams TN
Osier Faith HA
Nature Communications. 2022;134098
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/mul 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.
