Fibrinogen domain of FREP1 is a broad spectrum malaria transmission-blocking vaccine antigen

Guodong Niu; Caio Franca; Genwei Zhang; Wanlapa Roobsoong; Wang Nguitragool; Xiaohong Wang; Jetsumon Prachumsri; Noah S. Butler; Jun Li

doi:10.1074/jbc.M116.773564

Fibrinogen domain of FREP1 is a broad spectrum malaria transmission-blocking vaccine antigen

¹ Florida International University, United States;
² University of Oklahoma, United States;
³ Mahidol University Faculty of Tropical Medicine, Thailand;
⁴ University of Iowa, United States

↵* Corresponding author; email: lij{at}fiu.edu

Author contributions: GN and CF prepared proteins, vaccinated mice and infected mice and mosquitoes. GZ involved in infecting An. gambiae mosquitoes. WR and WN and JP designed and conducted experiments related to P. vivax and An. dirus. XW participated data analysis. NSB involved in experimental design and vaccinating mice. JL designed the project, conducted experiments, and analyzed the data. GN, CF and JL wrote the manuscripts. All edited the manuscript.

Abstract

FREP1 in mosquito midguts facilitates P. falciparum parasite transmission. 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 P. berghei and P. vivax to An. gambiae and An. dirus respectively. Furthermore, in vivo studies of mice immunized with FBG achieved >75% blocking efficacy of P. berghei to An. gambiae, without triggering immunopathology. Anti-FBG serum also reduced >81% P. falciparum infection to An. gambiae. Finally, we showed that FBG interacted 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 targeting FBG domain of FREP1 will limit the transmission of multiple Plasmodium species to multiple Anopheles species.