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, CHMI-SIKA Study Team, Faith H A Osier, 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 Mohammed, 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, 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, CHMI-SIKA Study Team, Faith H A Osier, 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 Mohammed, 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
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.
Conflict of interest statement
B.K.L.S., Y.A., P.F.B., S.L.H, E.R.J., TR. are salaried, full-time employees of Sanaria Inc., the manufacturer of Sanaria PfSPZ Challenge. Thus, all authors associated with Sanaria Inc. have potential conflicts of interest. All other authors declare no competing interests.
© 2022. The Author(s).
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References
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