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

作者：Niu Guodong; Franca Caio; Zhang Genwei; Roobsoong Wanlapa; Nguitragool Wang; Wang Xiaohong; Prachumsri Jetsumon; Butler Noah S; Li Jun^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2017, 292(28): 11960-11969.

DOI：10.1074/jbc.M116.773564

• infection
• ligand-binding protein
• malaria
• parasite
• vaccine
• malaria transmission-blocking vaccine

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.

• 出版日期2017-7-14