Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity.

Stone, WJR; Campo, JJ; Ouédraogo, AL; Meerstein-Kessel, L; Morlais, I; Da, D; Cohuet, A; Nsango, S; Sutherland, CJ; van de Vegte-Bolmer, M; Siebelink-Stoter, R; van Gemert, GJ; Graumans, W; Lanke, K; Shandling, AD; Pablo, JV; Teng, AA; Jones, S; de Jong, RM; Fabra-García, A; Bradley, J; Roeffen, W; Lasonder, E; Gremo, G; Schwarzer, E; Janse, CJ; Singh, SK; Theisen, M; Felgner, P; Marti, M; Drakeley, C; Sauerwein, R; Bousema, T; Jore, MM; (2018) Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity. Nature communications, 9 (1). p. 558. ISSN 2041-1723 DOI: https://doi.org/10.1038/s41467-017-02646-2

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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: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Malaria Centre
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PubMed ID: 29422648
Web of Science ID: 424451300003
URI: http://researchonline.lshtm.ac.uk/id/eprint/4646594


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