BACKGROUND:
Malaria remains a serious public health problem in Sub-Saharan Africa, with Plasmodium falciparum being the most common cause of morbidity and mortality, especially among children under the age of five. The goal of this study is to thoroughly examine the efficacy, safety, and immunogenicity of the R21/Matrix-M malaria vaccine in children in Sub-Saharan Africa.

METHODS:
A systematic review and meta-analysis were carried out in compliance with PRISMA 2020 recommendations. Between 2010 and 2025, six databases were searched for randomised controlled trials (RCTs) evaluating R21/Matrix-M in children aged 5-36 months. The outcomes of interest included vaccination effectiveness, adverse events, and anti-NANP antibody responses. The Cochrane RoB 2.0 tool was used to assess risk of bias, and pooled efficacy estimates were computed with a random-effects model.

RESULTS:
Four suitable RCTs with 5,952 children from Burkina Faso, Mali, Kenya, and Tanzania were included. The R21/Matrix-M vaccination reduced malaria incidence by 52% (RR = 0.48; 95% CI: 0.39-0.60). The 50 µg Matrix-M adjuvant formulation showed better efficacy (RR = 0.43; 95% CI: 0.34–0.54) than 25 µg Matrix-M (RR = 0.57; 95% CI: 0.46–0.71). The vaccine showed significant immunogenicity, with anti-NANP antibody titers exceeding 11,000 EU/mL after vaccination. The majority of adverse events were mild to moderate; significant adverse events were infrequent and unrelated to the vaccination. Antibody titers and protective effectiveness were maintained for up to 24 months with booster doses.