Malaria, which is the result of Plasmodium falciparum infection, is a global 
health threat that resulted in 655,000 deaths and 216 million clinical cases in 
2010 alone. Recent phase 3 trials with malaria vaccine candidate RTS,S/AS01 
(RTS,S) in children has demonstrated modest efficacy against clinical and severe 
malaria. RTS,S targets the pre-erythrocytic phase of the disease and induces 
high antibody titers against the P. falciparum circumsporozoite protein (CSP) 
and a moderate CD4(+) T cell response. The individual contribution of these 
adaptive immune responses to protection from infection remains unknown. Here, we 
found that prophylactic administration of anti-CSP mAbs derived from an 
RTS,S-vaccinated recipient fully protected mice with humanized livers from i.v.- 
and mosquito bite–delivered P. falciparum sporozoite challenge. Titers of 
anti-CSP that conveyed full protection were within the range observed in human 
RTS,S vaccine recipients. Increasing anti-CSP titers resulted in a 
dose-dependent reduction of the liver parasite burden. These data indicate that 
RTS,S-induced antibodies are protective and provide sterilizing immunity against 
P. falciparum infection when reaching or exceeding a critical plasma 
concentration.