A region of Plasmodium falciparum antigen Pfs25 that is the target of highly potent transmission-blocking antibodies

Each of the four epidermal growth factor (EGF)-like domains of the Plasmodi um falciparum sexual-stage antigen Pfs25 has been individually expressed as a yeast-secreted recombinant protein (yEGF1 through yEGF4). All four are r ecognized by the immune sera of animals and humans vaccinated with TBV25H ( the corresponding yeast-secreted full-length recombinant form of Pfs25), wi th antibody titers to yEGF1 and yEGF2 weakly correlating with the ability o f the sera to block the transmission of parasites to the mosquito host. All four proteins are poorly immunogenic in mice vaccinated with aluminum hydr oxide-absorbed formulations. However, all four successfully primed the mice to mount an effective secondary antibody response after a single boost wit h TBV25H, Sera from mice vaccinated with yEGF2-TBV25H completely block the development of oocysts in mosquito midguts in membrane-feeding assays. Furt her, of the four proteins, only the depletion of antibodies to yEGF2 from t he sera of rabbits vaccinated with TBV25H consistently abolished the abilit y of those sera to block oocyst development. Thus, antibodies to the second EGF-like domain of Pfs25 appear to mediate a very potent blocking activity , even at low titers, Vaccination strategies that target antibody response towards this domain may improve the efficacy of future transmission-blockin g vaccines.