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

• DOI: 10.1038/s41467-022-31640-6
• Publication Date: 2022-07-14T15:05:17Z
• Authors: 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; ; Abdirahman I. Abdi; Yonas Abebe; Philip Bejon; Peter F. Billingsley; Peter C. Bull; Zaydah de Laurent; Stephen L. Hoffman; Eric R. James; Silvia Kariuki; Rinter Kimathi; Sam Kinyanjui; Cheryl Kivisi; Johnstone Makale; Kevin Marsh; Khadija Said Moha...; Moses Mosobo; Janet Musembi; Jennifer Musyoki; Michelle Muthui; Jedidah Mwacharo; Francis Ndungu; Joyce M. Ngoi; Omar Ngoto; Bernhards Ogutu; Fredrick Olewe; Donwilliams Omuoyo; John Ong’echa; Edward Otieno; Jimmy Shangala; Betty Kim Lee Sim; Thomas L. Richie; Juliana Wambua; Thomas N. Williams; Faith H. A. Osier
• Keywords: Plasmodium (life cycle)

Abstract Ring-infected erythrocytes are the predominant asexual stage in peripheral circulation but rarely investigated context of acquired immunity against Plasmodium falciparum malaria. Here we compare antibody-dependent phagocytosis ring-infected parasite cultures samples from a controlled human malaria infection (CHMI) study (NCT02739763). Protected volunteers did not develop clinical symptoms, maintained parasitaemia below predefined threshold 500 parasites/μl and were treated until end study. Antibody-dependent both uninfected was strongly correlated with protection. A surface proteomic analysis revealed presence merozoite proteins including erythrocyte binding antigen-175 −140 on erythrocytes, providing an additional antibody-mediated protective mechanism for their activity beyond invasion-inhibition. Competition assays support hypothesis that antigens key mediators this functional activity. Targeting ring-stage parasites may contribute to control prevention