Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

Stone, W. J.R. et al. (2018) Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity. Nature Communications, 9, 558. (doi: 10.1038/s41467-017-02646-2) (PMID:29422648) (PMCID:PMC5805765)

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Infection with Plasmodium can elicit antibodies that inhibit parasite survival in the mosquito, when they are ingested in an infectious blood meal. Here, we determine the transmission-reducing activity (TRA) of naturally acquired antibodies from 648 malaria-exposed individuals using lab-based mosquito-feeding assays. Transmission inhibition is significantly associated with antibody responses to Pfs48/45, Pfs230, and to 43 novel gametocyte proteins assessed by protein microarray. In field-based mosquito-feeding assays the likelihood and rate of mosquito infection are significantly lower for individuals reactive to Pfs48/45, Pfs230 or to combinations of the novel TRA-associated proteins. We also show that naturally acquired purified antibodies against key transmission-blocking epitopes of Pfs48/45 and Pfs230 are mechanistically involved in TRA, whereas sera depleted of these antibodies retain high-level, complement-independent TRA. Our analysis demonstrates that host antibody responses to gametocyte proteins are associated with reduced malaria transmission efficiency from humans to mosquitoes.

Item Type:Articles
Additional Information:This work was supported by a Marie Curie Career Integration Grant from the European Community’s Seventh Framework Programme (SIGNAL, PCIG12-GA-2012-333936), and by a VIDI fellowship from the Netherlands Organization for Scientific Research (NWO; Project Number 016.158.306). Data collection in Burkina Faso was supported by the Bill and Melinda Gates Foundation (AFIRM OPP1034789). PfGEST mAb were produced by the Hypothesis-driven Pre-erythrocytic Antigen Target Identification Consortium (HPATIC) and provided by PATH’s malaria vaccine initiative. A correction to this article is available at https://doi.org/10.1038/s41467-018-03769-w.
Glasgow Author(s) Enlighten ID:Marti, Professor Matthias
Authors: Stone, W. J.R., Campo, J. J., Ouédraogo, A. L., Meerstein-Kessel, L., Morlais, I., Da, D., Cohuet, A., Nsango, S., Sutherland, C. J., van de Vegte-Bolmer, M., Siebelink-Stoter, R., van Gemert, G.-J., Graumans, W., Lanke, K., Shandling, A. D., Pablo, J. V., Teng, A. A., Jones, S., de Jong, R. M., Fabra-García, A., Bradley, J., Roeffen, W., Lasonder, E., Gremo, G., Schwarzer, E., Janse, C. J., Singh, S. K., Theisen, M., Felgner, P., Marti, M., Drakeley, C., Sauerwein, R., Bousema, T., and Jore, M. M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Nature Communications 9: 558
Publisher Policy:Reproduced under a Creative Commons License
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