Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Immunity to malaria has long been thought to be stage-specific. In this study we show that immunization of BALB/c mice with live erythrocytes infected with nonlethal strains of Plasmodium yoelii under curative chloroquine cover conferred protection not only against challenge by blood stage parasites but also against sporozoite challenge. This cross-stage protection was dose-dependent and long lasting. CD4(+) and CD8(+) T cells inhibited malaria liver but not blood stage. Their effect was mediated partially by IFN-gamma, and was completely dependent of NO. Abs against both pre-erythrocytic and blood parasites were elicited and were essential for protection against blood stage and liver stage parasites. Our results suggest that Ags shared by liver and blood stage parasites can be the foundation for a malaria vaccine that would provide effective protection against both pre-erythrocytic and erythrocytic asexual parasites found in the mammalian host. The Journal of Immunology, 2008, 181: 8552-8558.1811285528558Institut National de la Sante et de In Recherche MedicaleCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Minisetre de la Recherche et de la Technologie FranceJunta Nacional de Investigacao Cientifica e Tecnologica Portugal [BD/9255/96]National Institutes of Health [T32 A107180, R01 AI056840]Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CAPES [BEX 0446/98-0]Junta Nacional de Investigacao Cientifica e Tecnologica Portugal [BD/9255/96]National Institutes of Health [T32 A107180, R01 AI056840]