A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon.

Abstract

BACKGROUND: The malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion--based formulation (AS02) and a formulation based on liposomes (AS01). METHODS & PRINCIPAL FINDINGS: In this Phase II, double-blind study (NCT00307021), 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS,S/AS01(E) or RTS,S/AS02(D), on a 0-1-2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02(D)/AS01(E)) of 0.88 (95% CI: 0.68-1.15) post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated. CONCLUSIONS: RTS,S/AS01(E) proved similarly as well tolerated and immunogenic as RTS,S/AS02(D), completing an essential step in the age de-escalation process within the RTS,S clinical development plan. TRIAL REGISTRATION: ClinicalTrials.gov. NCT00307021.