Apical membrane antigen 1 (AMA1) is the one of the beststudied blood-stage vaccine candidates and it is an essential protein for parasite invasion of an erythrocyte [4] . The invasion process is complicated (i.e., initial attachment, reorientation, tight junction formation and internalization), and different studies have suggested different roles for AMA1: binding to erythrocytes [5] [6] [7] , reorientation [8] , or internalization [9] . In addition to erythrocyte invasion, a recent study suggests that AMA1 is involved in sporozoite invasion of hepatocytes [10] . These results indicate the AMA1 protein may have multiple roles. Many studies have shown that AMA1 vaccination can induce protective immunity in animal models (reviewed in [11] ) and in an Aotus monkey challenge model (the monkeys were challenged with P. falciparum). In the monkey challenge model, anti-AMA1 antibody levels induced by a vaccine before challenge have shown to correlate with protection [12, 13] . In addition to the animal data, many, but not all, epidemiological studies suggest a high level of AMA1 antibodies is associated with a reduced risk of malaria [11] . Based on these findings, multiple AMA1 Phase 1 trials [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] and a Phase 2 field trial [25] have been conducted and published. However, to date no significant protective effects have been shown in the target population of African children.