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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-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 | Matthijs M Jore
Nature communications | 2018

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.

Pubmed ID: 29422648

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: Medical Research Council, United Kingdom
    Id: MR/K012126/1

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GE Healthcare (tool)

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RRID:SCR_003411

Centralized, standards compliant, public data repository for proteomics data, including protein and peptide identifications, post-translational modifications and supporting spectral evidence. Originally it was developed to provide a common data exchange format and repository to support proteomics literature publications. This remit has grown with PRIDE, with the hope that PRIDE will provide a reference set of tissue-based identifications for use by the community. The future development of PRIDE has become closely linked to HUPO PSI. PRIDE encourages and welcomes direct user submissions of protein and peptide identification data to be published in peer-reviewed publications. Users may Browse public datasets, use PRIDE BioMart for custom queries, or download the data directly from the FTP site. PRIDE has been developed through a collaboration of the EMBL-EBI, Ghent University in Belgium, and the University of Manchester.

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RRID:SCR_004055

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RRID:SCR_010276

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RRID:SCR_012763

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