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.
Keywords:
infection; ligand-binding protein; malaria; malaria transmission–blocking vaccine; parasite; vaccine.
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Anopheles / immunology
-
Anopheles / metabolism*
-
Anopheles / parasitology
-
Antibodies, Blocking / analysis
-
Conserved Sequence
-
Female
-
Germ Cells / immunology
-
Germ Cells / metabolism
-
Humans
-
Insect Proteins / chemistry
-
Insect Proteins / genetics
-
Insect Proteins / metabolism
-
Insect Proteins / therapeutic use*
-
Malaria Vaccines / chemistry
-
Malaria Vaccines / genetics
-
Malaria Vaccines / metabolism
-
Malaria Vaccines / therapeutic use*
-
Malaria, Falciparum / immunology
-
Malaria, Falciparum / parasitology
-
Malaria, Falciparum / prevention & control*
-
Malaria, Falciparum / transmission
-
Malaria, Vivax / blood
-
Malaria, Vivax / immunology
-
Malaria, Vivax / parasitology
-
Male
-
Mice
-
Peptide Fragments / chemistry
-
Peptide Fragments / genetics
-
Peptide Fragments / metabolism
-
Peptide Fragments / therapeutic use
-
Plasmodium berghei / growth & development
-
Plasmodium berghei / immunology
-
Plasmodium falciparum / growth & development
-
Plasmodium falciparum / immunology*
-
Plasmodium vivax / growth & development
-
Plasmodium vivax / immunology
-
Protein Interaction Domains and Motifs
-
Recombinant Proteins / chemistry
-
Recombinant Proteins / metabolism
-
Recombinant Proteins / therapeutic use
-
Sequence Alignment
-
Sequence Homology, Amino Acid
-
Species Specificity
-
Vaccines, Synthetic / chemistry
-
Vaccines, Synthetic / metabolism
-
Vaccines, Synthetic / therapeutic use
Substances
-
Antibodies, Blocking
-
Insect Proteins
-
Malaria Vaccines
-
Peptide Fragments
-
Recombinant Proteins
-
Vaccines, Synthetic