The effect of the RTS,S/AS01E vaccine booster dose on cell-mediated immune responses in African infants and children

Abstract RTS,S/AS01E, the first approved malaria vaccine, demonstrated moderate efficacy during the phase 3 pediatric trial. We previously investigated cell-mediated immune (CMI) responses following the primary 3-dose immunizations and now report responses to the booster dose given 18 months later. Thirty CMI markers were measured by Luminex in lymphocytes from 709 children and infants following RTS,S/AS01E antigen stimulation, which were assessed for associations with malaria risk and antibodies one month post-booster and one year later. IL-2, IFN-γ, IL-17, IL-5, and IL-13 were associated with RTS,S/AS01E vaccination after booster, and IL-2 responses to circumsporozoite protein (CSP) remained higher after one year. IL-2 was associated with reduced malaria risk in one cohort, and IL-10 was associated with increased risk in infants. Anti-CSP IgG and IL-2 were moderately correlated one year after booster. This study highlights the moderate cell-mediated immunogenicity of the RTS,S/AS01E booster dose that aligns with partial recovery of RTS,S/AS01E vaccine efficacy.