Antibodies to a Single, Conserved Epitope in AnophelesAPN1 Inhibit Universal Transmission of Plasmodium falciparumand Plasmodium vivaxMalaria

Autor: Armistead, Jennifer S., Morlais, Isabelle, Mathias, Derrick K., Jardim, Juliette G., Joy, Jaimy, Fridman, Arthur, Finnefrock, Adam C., Bagchi, Ansu, Plebanski, Magdalena, Scorpio, Diana G., Churcher, Thomas S., Borg, Natalie A., Sattabongkot, Jetsumon, Dinglasan, Rhoel R.
Zdroj: Infection and Immunity; December 2013, Vol. 82 Issue: 2 p818-829, 12p
Abstrakt: ABSTRACTMalaria 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 Plasmodiumparasite, the Anophelesmosquito. In this study, we demonstrated that antibodies targeting AnAPN1 block transmission of Plasmodium falciparumand Plasmodium vivaxacross 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.
Databáze: Supplemental Index