Abstract
Phagocytosis of Plasmodium falciparum ring-stage parasites predicts protection against malaria
Musasia, F. K.
Nkumama, I. N.
Frank, R.
Kipkemboi, V.
Schneider, M.
Mwai, K.
Odera, D. O.
Rosenkranz, M.
F├╝rle, K.
Kimani, D.
Tuju, J.
Njuguna, P.
Hamaluba, M.
Kapulu, M. C.
Wardemann, H.
Abdi, A. I.
Abebe, Y.
Bejon, P.
Billingsley, P. F.
Bull, P. C.
de Laurent, Z.
Hoffman, S. L.
James, E. R.
Kariuki, S.
Kimathi, R.
Kinyanjui, S.
Kivisi, C.
Makale, J.
Marsh, K.
Mohammed, K. S.
Mosobo, M.
Musembi, J.
Musyoki, J.
Muthui, M.
Mwacharo, J.
Ndungu, F.
Ngoi, J. M.
Ngoto, O.
Ogutu, B.
Olewe, F.
Omuoyo, D.
OngÔÇÖecha, J.
Otieno, E.
Shangala, J.
Sim, B. K. L.
Richie, T. L.
Wambua, J.
Williams, T. N.
Osier, F. H. A.
Nature Communications. 2022; 134098
Permanent descriptor
https://doi.org/10.1038/s41467-022-31640-6Ring-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.
