| Literature DB >> 28533429 |
Guodong Niu1, Caio Franc A2, Genwei Zhang2, Wanlapa Roobsoong3, Wang Nguitragool3, Xiaohong Wang1, Jetsumon Prachumsri3, Noah S Butler4, Jun Li5,2.
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.Entities:
Keywords: infection; ligand-binding protein; malaria; malaria transmission–blocking vaccine; parasite; vaccine
Mesh：
Substances：
Year: 2017 PMID： 28533429 PMCID： PMC5512087 DOI： 10.1074/jbc.M116.773564
Source DB: PubMed Journal: J Biol Chem ISSN： 0021-9258 Impact factor: 5.157