Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

Will J.R. Stone*, Joseph J. Campo, André Lin Ouédraogo, Lisette Meerstein-Kessel, Isabelle Morlais, Dari Da, Anna Cohuet, Sandrine Nsango, Colin J. Sutherland, Marga Van De Vegte-Bolmer, 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-GarcíaJohn Bradley, Will Roeffen, Edwin Lasonder, Giuliana Gremo, Evelin Schwarzer, Chris J. Janse, Susheel K. Singh, Michael Theisen, Phil Felgner, Matthias Marti, Chris Drakeley, Robert Sauerwein, Teun Bousema, Matthijs M. Jore

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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.

Original languageEnglish
Article number558
Number of pages14
JournalNature Communications
Volume9
Issue number1
Early online date8 Feb 2018
DOIs
Publication statusPublished - 1 Dec 2018
Externally publishedYes

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