Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

Stone, Will J. R., Campo, Joseph J., Ouédraogo, André Lin, Meerstein-Kessel, Lisette, Morlais, Isabelle, Da, Dari, Cohuet, Anna, Nsango, Sandrine, Sutherland, Colin J., van de Vegte-Bolmer, Marga, Siebelink-Stoter, Rianne, van Gemert, Geert-Jan, Graumans, Wouter, Lanke, Kjerstin, Shandling, Adam D., Pablo, Jozelyn V., Teng, Andy A., Jones, Sophie, de Jong, Roos M., Fabra-García, Amanda, Bradley, John, Roeffen, Will, Lasonder, Edwin, Gremo, Giuliana, Schwarzer, Evelin, Janse, Chris J., Singh, Susheel K., Theisen, Michael, Felgner, Phil, Marti, Matthias, Drakeley, Chris, Sauerwein, Robert, Bousema, Teun and Jore, Matthijs M. (2018) Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity. Nature Communications, 9 (1). p. 558. ISSN 2041-1723

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Abstract

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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