Naturally acquired immunity against immature Plasmodium falciparum gametocytes

Dantzler, K. W. et al. (2019) Naturally acquired immunity against immature Plasmodium falciparum gametocytes. Science Translational Medicine, 11(495), eaav3963. (doi: 10.1126/scitranslmed.aav3963) (PMID:31167926) (PMCID:PMC6653583)

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The recent decline in global malaria burden has stimulated efforts toward Plasmodium falciparum elimination. Understanding the biology of malaria transmission stages may provide opportunities to reduce or prevent onward transmission to mosquitoes. Immature P. falciparum transmission stages, termed stages I to IV gametocytes, sequester in human bone marrow before release into the circulation as mature stage V gametocytes. This process likely involves interactions between host receptors and potentially immunogenic adhesins on the infected red blood cell (iRBC) surface. Here, we developed a flow cytometry assay to examine immune recognition of live gametocytes of different developmental stages by naturally exposed Malawians. We identified strong antibody recognition of the earliest immature gametocyte-iRBCs (giRBCs) but not mature stage V giRBCs. Candidate surface antigens (n = 30), most of them shared between asexual- and gametocyte-iRBCs, were identified by mass spectrometry and mouse immunizations, as well as correlations between responses by protein microarray and flow cytometry. Naturally acquired responses to a subset of candidate antigens were associated with reduced asexual and gametocyte density, and plasma samples from malaria-infected individuals were able to induce immune clearance of giRBCs in vitro. Infected RBC surface expression of select candidate antigens was validated using specific antibodies, and genetic analysis revealed a subset with minimal variation across strains. Our data demonstrate that humoral immune responses to immature giRBCs and shared iRBC antigens are naturally acquired after malaria exposure. These humoral immune responses may have consequences for malaria transmission potential by clearing developing gametocytes, which could be leveraged for malaria intervention.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Ngotho, Dr Priscilla and Marti, Professor Matthias and Seydel, Dr Karl and Lemgruber Soares, Dr Leandro and De Niz, Dr Mariana
Authors: Dantzler, K. W., Ma, S., Ngotho, P., Stone, W. J.R., Tao, D., Rijpma, S., De Niz, M., Nilsson Bark, S. K., Jore, M. M., Raaijmakers, T. K., Early, A. M., Ubaida-Mohien, C., Lemgruber, L., Campo, J. J., Teng, A. A., Le, T. Q., Walker, C. L., Hermand, P., Deterre, P., Davies, D. H., Felgner, P., Morlais, I., Wirth, D. F., Neafsey, D. E., Dinglasan, R. R., Laufer, M., Huttenhower, C., Seydel, K., Taylor, T., Bousema, T., and Marti, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Science Translational Medicine
Publisher:American Association for the Advancement of Science
ISSN (Online):1946-6242
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Science Translational Medicine 11(495):eaav3963
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
371799The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/Z & AIII - PARASITOLOGY
678901EPSRC DTG 2014Mary Beth KneafseyEngineering and Physical Sciences Research Council (EPSRC)EP/M506539/1R&I - RESEARCH STRATEGY & INNOVATION