The Virtues and Vices of Pfs230: From Vaccine Concept to Vaccine Candidate

Abstract

Among the Plasmodium falciparum surface antigens reported by Richard Carter and his colleagues decades ago, Pfs230 is currently the target of the most advanced candidate for a malaria transmission-blocking vaccine. First identified by its orthologue in the avian malaria parasite Plasmodium gallinaceum, the large cysteine-rich 14-domain Pfs230 antigen is displayed on the surface of gametes that emerge in the mosquito midgut. Gametes lacking Pfs230 cannot bind to red blood cells nor develop further into oocysts. Human antibodies against Pfs230 lyse gametes in the presence of complement, which largely explains serum transmission-blocking activity in Pfs230 antisera. A protein-protein conjugate vaccine that incorporates the first domain of the Pfs230 antigen induced greater serum transmission-reducing activity versus a similarly manufactured Pfs25 vaccine in U.S. trials, and is currently in phase II field trials in Mali.