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

Will JR Stone ORCID logo ; Joseph J Campo ; André Lin Ouédraogo ; Lisette Meerstein-Kessel ; Isabelle Morlais ; Dari Da ; Anna Cohuet ORCID logo ; Sandrine Nsango ; Colin J Sutherland ORCID logo ; Marga van de Vegte-Bolmer ; +24 more... Rianne Siebelink-Stoter ; Geert-Jan van Gemert ; Wouter Graumans ; Kjerstin Lanke ; Adam D Shandling ; Jozelyn V Pablo ; Andy A Teng ; Sophie Jones ; Roos M de Jong ; Amanda Fabra-García ; John Bradley ORCID logo ; Will Roeffen ; Edwin Lasonder ; Giuliana Gremo ; Evelin Schwarzer ORCID logo ; Chris J Janse ; Susheel K Singh ; Michael Theisen ; Phil Felgner ; Matthias Marti ; Chris Drakeley ORCID logo ; Robert Sauerwein ; Teun Bousema ; Matthijs M Jore ; (2017) Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity. Nature communications, 9 (1). 558-. ISSN 2041-1723 DOI: 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.


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