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Title: The fibrinogen-like domain of FREP1 protein is a broad-spectrum malaria transmission-blocking vaccine antigen
Authors: Guodong Niu
Caio França
Genwei Zhang
Wanlapa Roobsoong
Wang Nguitragool
Xiaohong Wang
Jetsumon Prachumsri
Noah S. Butler
Jun Li
University of Oklahoma
Mahidol University
University of Iowa
Florida International University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 14-Jul-2017
Citation: Journal of Biological Chemistry. Vol.292, No.28 (2017), 11960-11969
Abstract: © 2017 by The American Society for Biochemistry and Molecular Biology, Inc. FREP1 in mosquito midguts facilitates Plasmodium falciparum parasite transmission. The fibrinogen-like (FBG) domain of FREP1 is highly conserved (>90% identical) among Anopheles species from different continents, suggesting that anti-FBG antibodies may block malaria transmission to all anopheline mosquitoes. Using standard membrane-feeding assays, anti-FREP1 polyclonal antibodies significantly blocked transmission of Plasmodium berghei and Plasmodium vivax to Anopheles gambiae and Anopheles dirus, respectively. Furthermore, in vivo studies of mice immunized with FBG achieved >75% blocking efficacy of P. berghei to A. gambiae without triggering immunopathology. Anti-FBG serum also reduced >81% of P. falciparum infection to A. gambiae. Finally, we showed that FBG interacts with Plasmodium gametocytes and ookinetes, revealing the molecular mechanism of its antibody transmission-blocking activity. Collectively, our data support that FREP1-mediated Plasmodium transmission to mosquitoes is a conserved pathway and that targeting the FBG domain of FREP1 will limit the transmission of multiple Plasmodium species to multiple Anopheles species.
ISSN: 1083351X
Appears in Collections:Scopus 2016-2017

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