Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

نویسندگان

  • 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
چکیده

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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عنوان ژورنال:

دوره 9  شماره 

صفحات  -

تاریخ انتشار 2018