Protection against Plasmodium falciparum malaria in chimpanzees by immunization with the conserved preerythrocytic liver-stage antigen 3

In humans, sterile immunity against malaria can be consistently induced thr ough exposure to the bites of thousands of irradiated infected mosquitoes. The same level of protection has yet to be achieved using subunit vaccines. Recent studies have indicated an essential function for intrahepatic paras ites, the stage after the mosquito bite, and thus for antigens expressed du ring this stage. We report here the identification of liver-stage antigen 3 , which is expressed both in the mosquito and liver-stage parasites. This P lasmodium falciparum 200-kilodalton protein is highly conserved, and showed promising antigenic and immunogenic properties. In chimpanzees (Pan troglo dytes), the primates most closely related to humans and that share a simila r susceptibility to P. falciparum liver-stage infection, immunization with LSA-3 induced protection against successive heterologous challenges with la rge numbers of P. falciparum sporozoites.