Antibodies to a single, conserved epitope in Anopheles APN1 inhibit universal transmission of Plasmodium falciparum and Plasmodium vivax malaria.
Malaria transmission-blocking vaccines (TBVs) represent a promising approach for the elimination and eradication of this disease. AnAPN1 is a lead TBV candidate that targets a surface antigen on the midgut of the obligate vector of the Plasmodium parasite, the Anopheles mosquito. In this study, we demonstrated that antibodies targeting AnAPN1 block transmission of Plasmodium falciparum and Plasmodium vivax across distantly related anopheline species in countries to which malaria is endemic. Using a biochemical and immunological approach, we determined that the mechanism of action for this phenomenon stems from antibody recognition of a single protective epitope on AnAPN1, which we found to be immunogenic in murine and nonhuman primate models and highly conserved among anophelines. These data indicate that AnAPN1 meets the established target product profile for TBVs and suggest a potential key role for an AnAPN1-based panmalaria TBV in the effort to eradicate malaria.
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health and the Malaria Research Institute, Baltimore, Maryland, USA.
Jennifer S
JS
Armistead
Isabelle
I
Morlais
Derrick K
DK
Mathias
Juliette G
JG
Jardim
Jaimy
J
Joy
Arthur
A
Fridman
Adam C
AC
Finnefrock
Ansu
A
Bagchi
Magdalena
M
Plebanski
Diana G
DG
Scorpio
Thomas S
TS
Churcher
Natalie A
NA
Borg
Jetsumon
J
Sattabongkot
Rhoel R
RR
Dinglasan
D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D005260:Female; D019476:Insect Proteins / Q000008:administration & dosage / Q000276:immunology*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control* / Q000635:transmission; D016780:Malaria, Vivax / Q000517:prevention & control* / Q000635:transmission; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D019476:Insect Proteins; D017780:Malaria Vaccines