Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial

Methods From March 27, 2009, until Jan 31, 2011, children (age 5–17 months) and young infants (age 6–12 weeks) were enrolled at 11 centres in seven countries in sub-Saharan Africa. Participants were randomly assigned (1:1:1) at fi rst vaccination by block randomisation with minimisation by centre to receive three doses of RTS,S/AS01 at months 0, 1, and 2 and a booster dose at month 20 (R3R group); three doses of RTS,S/AS01 and a dose of comparator vaccine at month 20 (R3C group); or a comparator vaccine at months 0, 1, 2, and 20 (C3C [control group]). Participants were followed up until Jan 31, 2014. Cases of clinical and severe malaria were captured through passive case detection. Serious adverse events (SAEs) were recorded. Analyses were by modifi ed intention to treat and per protocol. The coprimary endpoints were the occurrence of malaria over 12 months after dose 3 in each age category. In this fi nal analysis, we present data for the effi cacy of the booster on the occurrence of malaria. Vaccine effi cacy (VE) against clinical malaria was analysed by negative binomial regression and against severe malaria by relative risk reduction. This trial is registered with ClinicalTrials.gov, number NCT00866619.