Four doses of RTS,S/AS01 or R21/Matrix-M malaria vaccines provide added protection through early childhood, the period of highest risk of severe malaria in moderate-to-high-transmission settings.
Data show RTS,S/AS01 efficacy against clinical and severe malaria is highest in the first six months after the third dose, then wanes over time until a fourth dose is given 18 months later. Go to footnote 1, Go to footnote 2 The fourth dose extends protection but does not restore to highest efficacy. Protection against clinical malaria persists for up to seven years in children who received three or four doses, whereas sustained protection against severe malaria requires all four doses. Go to footnote 3 There is no evidence of severe malaria rebound in children who received only three doses. Go to footnote 4 When administered seasonally with Seasonal Malaria Chemoprevention (SMC), RTS,S/AS01 (up to seven doses) confers substantial and sustained protection against clinical and severe malaria for over five years. Go to footnote 5
Data show R21/Matrix M demonstrates high efficacy against clinical malaria the first six months after the third dose, with minimal waning observed until the fourth dose was given 12 months later. Long term follow up of Phase-3 study sites using age-based and seasonal approaches is ongoing. Go to footnote 6
- Go back to footnote reference 1
World Health Organization (2024). Malaria vaccines: WHO position paper, May 2024. Wkly Epidemiol Rec. 99(19):225–248 (https://www.who.int/publications/i/item/who-wer-9919-225-248, accessed 13 May 2026).
- Go back to footnote reference 2
RTS,S Clinical Trials Partnership. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet. 2015;386(9988):31–45. doi:10.1016/S0140-6736(15)60721-8.
- Go back to footnote reference 3
Tinto H, Otieno W, Gesase S, Sorgho H, Otieno L et al. Long-term incidence of severe malaria following RTS,S/AS01 vaccination in children and infants in Africa: an open-label 3-year extension study of a phase 3 randomised controlled trial. Lancet Infect Dis. 2019;19(8):821–832. doi:10.1016/S1473-3099(19)30300-7.
- Go back to footnote reference 4
World Health Organization (2025). Meeting of the Strategic Advisory Group of Experts on Immunization, September 2025: conclusions and recommendations, 5 December 2025. Wkly Epidemiol Rec. 100(49):661–700 (https://iris.who.int/handle/10665/384559, accessed 13 May 2026).
- Go back to footnote reference 5
Dicko A, Ouedraogo J-B, Zongo I, Sagara I, Cairns M et al. Seasonal vaccination with RTS,S/AS01E vaccine with or without seasonal malaria chemoprevention in children up to the age of 5 years in Burkina Faso and Mali: a double-blind, randomised, controlled, phase 3 trial. Lancet Infect Dis. 2024;24(1):75–86. doi:10.1016/S1473-3099(23)00368-7.
- Go back to footnote reference 6
World Health Organization (2024). Full evidence report on the R21/Matrix-M malaria vaccine. Geneva: World Health Organization (https://zenodo.org/records/10908560, accessed 19 January 2026).
