The acquisition of humoral immune responses targeting Plasmodium falciparum sexual stages in controlled human malaria infections

de Jong, R. M. et al. (2022) The acquisition of humoral immune responses targeting Plasmodium falciparum sexual stages in controlled human malaria infections. Frontiers in Immunology, 13, 930956. (doi: 10.3389/fimmu.2022.930956) (PMID:35924245) (PMCID:PMC9339717)

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Individuals infected with P. falciparum develop antibody responses to intra-erythrocytic gametocyte proteins and exported gametocyte proteins present on the surface of infected erythrocytes. However, there is currently limited knowledge on the immunogenicity of gametocyte antigens and the specificity of gametocyte-induced antibody responses. In this study, we assessed antibody responses in participants of two controlled human malaria infection (CHMI) studies by ELISA, multiplexed bead-based antibody assays and protein microarray. By comparing antibody responses in participants with and without gametocyte exposure, we aimed to disentangle the antibody response induced by asexual and sexual stage parasites. We showed that after a single malaria infection, a significant anti-sexual stage humoral response is induced in malaria-naïve individuals, even after exposure to relatively low gametocyte densities (up to ~1,600 gametocytes/mL). In contrast to antibody responses to well-characterised asexual blood stage antigens that were detectable by day 21 after infection, responses to sexual stage antigens (including transmission blocking vaccine candidates Pfs48/45 and Pfs230) were only apparent at 51 days after infection. We found antigens previously associated with early gametocyte or anti-gamete immunity were highly represented among responses linked with gametocyte exposure. Our data provide detailed insights on the induction and kinetics of antibody responses to gametocytes and identify novel antigens that elicit antibody responses exclusively in individuals with gametocyte exposure. Our findings provide target identification for serological assays for surveillance of the malaria infectious reservoir, and support vaccine development by describing the antibody response to leading vaccine antigens after primary infection.

Item Type:Articles
Additional Information:Funding: This work was supported by a Sir Henry Wellcome fellowship (number 218676/Z/19/Z) from the Wellcome Trust (UK) awarded to WS. TB, RMdJ and MA are supported by a fellowship from the European Research Council (ERC-CoG 864180; QUANTUM). CD and TO are supported by a project grant from the Bill and Melinda Gates foundation (INDIE OPP1173572), and KKAT is supported by the Intellectual Ventures Global Good Fund and a UKRI Connecting Capabilities fund/Bloomsbury SET (CCF-17-7779). MM and PN are supported by a Programme grant from the UKRI Medical Research Council (MR/T016272/1) and Wellcome Center award 104111.
Keywords:Immunology, malaria, Plasmodium falciparum, sexual stage, gametocyte antigens, antibody responses, controlled human malaria infection (CHMI)
Glasgow Author(s) Enlighten ID:Ngotho, Dr Priscilla and Marti, Professor Matthias
Authors: de Jong, R. M., Alkema, M., Oulton, T., Dumont, E., Teelen, K., Nakajima, R., de Assis, R. R., Press, K. W. D., Ngotho, P., Tetteh, K. K.A., Felgner, P., Marti, M., Collins, K. A., Drakeley, C., Bousema, T., and Stone, W. J.R.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Frontiers in Immunology
Publisher:Frontiers Media
ISSN (Online):1664-3224
Copyright Holders:Copyright © 2022 de Jong, Alkema, Oulton, Dumont, Teelen, Nakajima, de Assis, Press, Ngotho, Tetteh, Felgner, Marti, Collins, Drakeley, Bousema and Stone
First Published:First published in Frontiers in Immunology 13: 930956
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
307712Utilizing gametocyte immunity to reduce malaria transmissionMatthias MartiMedical Research Council (MRC)MR/T016272/1III - Parasitology