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 - 2018/12/1
Y1 - 2018/12/1
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 - http://www.scopus.com/inward/record.url?scp=85041955114&partnerID=8YFLogxK
UR - https://pearl.plymouth.ac.uk/handle/10026.1/10770
U2 - 10.1038/s41467-017-02646-2
DO - 10.1038/s41467-017-02646-2
M3 - Article
C2 - 29422648
AN - SCOPUS:85041955114
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 558
ER -
