Guodong NiuCaio FrançaGenwei ZhangWanlapa RoobsoongWang NguitragoolXiaohong WangJetsumon PrachumsriNoah S. ButlerJun LiUniversity of OklahomaMahidol UniversityUniversity of IowaFlorida International University2018-12-212019-03-142018-12-212019-03-142017-07-14Journal of Biological Chemistry. Vol.292, No.28 (2017), 11960-119691083351X002192582-s2.0-85023605528https://repository.li.mahidol.ac.th/handle/20.500.14594/41840© 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1074/jbc.M116.773564