RTS,S/AS01 mRNA Booster Platforms for Sustaining Protective Immunity Against Plasmodium Falciparum in African Children

Malaria caused by Plasmodium falciparum remained a leading cause of morbidity and mortality among African children, with hundreds of thousands of paediatric deaths annually despite expanded control measures. The RTS,S/AS01 pre-erythrocytic vaccine had demonstrated moderate efficacy, reducing clinical malaria episodes by approximately 45–50% in children aged 5–17 months, but protection wanes over time and is substantially lower in young infants, underscoring the need for strategies that sustain and amplify vaccine-induced immunity. This narrative review exploreed emerging concepts around RTS,S/AS01 mRNA booster platforms as a means to prolong protective immunity against P. falciparum in African children, integrating current evidence on RTS,S/AS01 performance, mRNA vaccine immunobiology, and booster strategies in high-transmission settings. A narrative review methodology was employed, drawing from randomized trials, implementation studies, and mRNA vaccine literature indexed in major databases up to mid-2026. Findings from phase 3 trials revealed that RTS,S/AS01 efficacy is enhanced by a fourth booster dose and by seasonal schedules combined with chemoprevention, but long-term protection remains incomplete. Parallel advances in mRNA technology suggested that mRNA-encoded circumsporozoite antigen boosters could re-engage B and T cell memory more flexibly and repeatedly, potentially overcoming waning immunity while enabling rapid adaptation to parasite antigenic variation. RTS,S/AS01 mRNA booster platforms represented a promising, though still theoretical, avenue for sustaining protective immunity against P. falciparum in African children, contingent on solving challenges of cost, cold-chain logistics, and equitable access. Keywords: RTS,S/AS01, Malaria vaccine, mRNA booster, Plasmodium falciparum, African children.