TY - JOUR

T1 - Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

AU - Stone, Will J R

AU - Campo, Joseph J

AU - Ouédraogo, André Lin

AU - Meerstein-Kessel, Lisette

AU - Morlais, Isabelle

AU - Da, Dari

AU - Cohuet, Anna

AU - Nsango, Sandrine

AU - Sutherland, Colin J

AU - van de Vegte-Bolmer, Marga

AU - Siebelink-Stoter, Rianne

AU - van Gemert, Geert-Jan

AU - Graumans, Wouter

AU - Lanke, Kjerstin

AU - Shandling, Adam D

AU - Pablo, Jozelyn V

AU - Teng, Andy A

AU - Jones, Sophie

AU - de Jong, Roos M

AU - Fabra-García, Amanda

AU - Bradley, John

AU - Roeffen, Will

AU - Lasonder, Edwin

AU - Gremo, Giuliana

AU - Schwarzer, Evelin

AU - Janse, Chris J

AU - Singh, Susheel K

AU - Theisen, Michael

AU - Felgner, Phil

AU - Marti, Matthias

AU - Drakeley, Chris

AU - Sauerwein, Robert

AU - Bousema, Teun

AU - Jore, Matthijs M

PY - 2018/2/8

Y1 - 2018/2/8

N2 - 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.

AB - 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.

UR - https://www.nature.com/articles/s41467-018-03769-w

U2 - 10.1038/s41467-017-02646-2

DO - 10.1038/s41467-017-02646-2

M3 - Journal article

C2 - 29422648

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 558

ER -