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 Vegte-Bolmer, Rianne Siebelink-Stoter, Geert-Jan Gemert, Wouter Graumans, Kjerstin Lanke, Adam D. Shandling, Jozelyn V. Pablo, Andy A. Teng, Sophie Jones, Roos M. Jong, Amanda Fabra-García, John 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 () and Matthijs M. Jore
Additional contact information
Will J. R. Stone: Radboud University Medical Center
Joseph J. Campo: Antigen Discovery Inc.
André Lin Ouédraogo: Institute for Disease Modeling
Lisette Meerstein-Kessel: Radboud University Medical Center
Isabelle Morlais: Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale
Dari Da: Institut de Recherche en Sciences de la Santé
Anna Cohuet: MIVEGEC (IRD, CNRS, Univ. Montpellier)
Sandrine Nsango: Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale
Colin J. Sutherland: London School of Hygiene and Tropical Medicine
Marga Vegte-Bolmer: Radboud University Medical Center
Rianne Siebelink-Stoter: Radboud University Medical Center
Geert-Jan Gemert: Radboud University Medical Center
Wouter Graumans: Radboud University Medical Center
Kjerstin Lanke: Radboud University Medical Center
Adam D. Shandling: Antigen Discovery Inc.
Jozelyn V. Pablo: Antigen Discovery Inc.
Andy A. Teng: Antigen Discovery Inc.
Sophie Jones: London School of Hygiene and Tropical Medicine
Roos M. Jong: Radboud University Medical Center
Amanda Fabra-García: Radboud University Medical Center
John Bradley: London School of Hygiene and Tropical Medicine
Will Roeffen: Radboud University Medical Center
Edwin Lasonder: Drakes Circus
Giuliana Gremo: University of Torino
Evelin Schwarzer: University of Torino
Chris J. Janse: Leiden University Medical Center (LUMC)
Susheel K. Singh: Statens Serum Institut
Michael Theisen: Statens Serum Institut
Phil Felgner: University of California Irvine
Matthias Marti: Harvard School of Public Health
Chris Drakeley: London School of Hygiene and Tropical Medicine
Robert Sauerwein: Radboud University Medical Center
Teun Bousema: Radboud University Medical Center
Matthijs M. Jore: Radboud University Medical Center

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-017-02646-2

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