Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination: A Phase 3 Randomized, Controlled Trial in Children and Young Infants at 11 African Sites

摘要: Background A malaria vaccine could be an important addition to current control strategies. We report the safety and efficacy (VE) of RTS,S/AS01 during 18 mo following vaccination at 11 African sites with varying transmission. Methods Findings 6,537 infants aged 6–12 wk 8,923 children 5–17 were randomized receive three doses or comparator vaccine. VE against clinical in after dose 3 (per protocol) was 46% (95% CI 42% 50%) (range 40% 77%; VE, p<0.01 across all sites). VE 20 1 (intention treat [ITT]) 45% 41% 49%). severe malaria, hospitalization, all-cause hospitalization 34% 15% 48%), 30% 50%), 19% 11% 27%), respectively (ITT). VE 27% 20% 32%, per protocol; [95% 21% 33%], ITT), no significant protection hospitalization. Post-vaccination anti-circumsporozoite antibody geometric mean titer varied from 348 787 EU/ml 117 335 protocol). VE waned over time both age categories (Schoenfeld residuals p<0.001). The number cases averted 1,000 vaccinated ranged 37 2,365 −1 49, respectively; corresponding ranges among −10 1,402 −13 37, (ITT). Meningitis reported as a serious adverse event 16/5,949 1/2,974 9/4,358 3/2,179 groups, respectively. Conclusions RTS,S/AS01 prevented many 3, highest impact areas greatest incidence. higher than infants, but even modest levels substantial. Africa.