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

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.

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