Efficacy and safety of RTS, S and R21 malaria vaccines in children under five in Africa: a systematic review and meta-analysis of randomized controlled trials

Abstract

Abstract Background Malaria remains a major public health burden in Africa, particularly among children under five years of age. By consolidating findings across randomized controlled trials on the RTS,S and R21 malaria vaccines, this study seeks to provide an evidence based guide. Methods We conducted a systematic review and meta-analysis of studies of randomized controlled trials evaluating the RTS,S and R21 malaria vaccines in African children under five. Data sources included PubMed, Scopus, and Embase. Primary outcomes were the vaccine efficacies against first/only episodes of malaria, multiple episodes and severe malaria; and the incidence of severe adverse events following vaccination. Pooled effect estimates were calculated using random-effects models. Results Eleven studies enrolling 27,178 participants (RTS,S: 21,589; R21: 5589) were included. For RTS,S, pooled efficacy against first clinical malaria episode was 32% (HR 0.68, 95% CI 0.61–0.76; I 2 = 0%), against multiple episodes was 29% (IRR 0.71, 95% CI 0.55–0.91; I 2 = 11.3%), and against severe malaria was 17–22% (RR 0.78–0.83). The R21 vaccine demonstrated 68% efficacy against first episodes (HR 0.32, 95% CI 0.26–0.39) and 67% against multiple episodes (IRR 0.33, 95% CI 0.27–0.41) in a single phase 3 trial. Pooled SAE incidence was 11.2% (95% CI 6.6–18.6%; I 2 = 96.2%) for RTS,S and 3% (95% CI 1–6%; I 2 = 80.6%) for R21, with no vaccine-attributable deaths. Both vaccines showed acceptable reactogenicity profiles. Conclusion Both RTS,S and R21 vaccines demonstrate protective efficacy against clinical malaria in African children under five, with R21 showing higher efficacy in initial trials. RTS,S provides moderate, reproducible protection in clinical trials. Both vaccines have acceptable safety profiles, though continued pharmacovigilance is essential.