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

Fauzia K. Musasia, Irene N. Nkumama, Roland Frank, Victor Kipkemboi, Martin Schneider, Kennedy Mwai, Dennis O. Odera, Micha Rosenkranz, Kristin Fürle, Domitila Kimani, James Tuju, Patricia Njuguna, Mainga Hamaluba, Melissa C. Kapulu, Hedda Wardemann and Faith H. A. Osier ()
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Fauzia K. Musasia: Heidelberg University Hospital
Irene N. Nkumama: Heidelberg University Hospital
Roland Frank: Heidelberg University Hospital
Victor Kipkemboi: Heidelberg University Hospital
Martin Schneider: German Cancer Research Center
Kennedy Mwai: Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme
Dennis O. Odera: Heidelberg University Hospital
Micha Rosenkranz: Heidelberg University Hospital
Kristin Fürle: Heidelberg University Hospital
Domitila Kimani: Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme
James Tuju: Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme
Patricia Njuguna: Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme
Mainga Hamaluba: Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme
Melissa C. Kapulu: Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme
Hedda Wardemann: German Cancer Research Center
Faith H. A. Osier: Heidelberg University Hospital

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31640-6

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