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J Biol Chem. 2017 Jul 14;292(28):11960-11969. doi: 10.1074/jbc.M116.773564. Epub 2017 May 22.

The fibrinogen-like domain of FREP1 protein is a broad-spectrum malaria transmission-blocking vaccine antigen.

Author information

1
the Department of Biological Sciences, Florida International University, Miami, Florida 33199.
2
From the Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019.
3
the Mahidol Vivax Research Center, Mahidol University Faculty of Tropical Medicine, Bangkok 10400, Thailand.
4
the Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa 52242, and.
5
the Department of Biological Sciences, Florida International University, Miami, Florida 33199 lij@fiu.edu.

Abstract

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.

KEYWORDS:

infection; ligand-binding protein; malaria; malaria transmission–blocking vaccine; parasite; vaccine

PMID:
28533429
PMCID:
PMC5512087
DOI:
10.1074/jbc.M116.773564
[Indexed for MEDLINE]
Free PMC Article

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