Clinical trials of age-based delivery of RTS,S and R21 vaccines showed more than 50% reduction in malaria cases over the first year of follow up, and prolonged protection with the fourth dose. Go to footnote 1, Go to footnote 2, Go to footnote 3, Go to footnote 4 WHO re-affirmed its recommendation for the 4-dose schedule after a case-control study showed the fourth dose provides 30% incremental effectiveness against severe malaria compared to three doses. Go to footnote 5
An independent evaluation of RTS,S/AS01 pilot implementation in childhood immunization in three African countries during a 46-month period showed a 13% drop in mortality from all causes among children age-eligible for vaccination, and a substantial reduction (22%) in hospitalizations for severe malaria. Go to footnote 6
About 75% reduction of malaria cases was achieved over the first year of follow up when malaria vaccines were given seasonally, just prior to the start of the high transmission season, and prolonged protection with annual seasonal doses. Go to footnote 7
The WHO recommendation for R21/Matrix-M was based on the similar vaccine construct as RTS,S/AS01 and results from an ongoing trial that showed similar high vaccine efficacy across sites using age-based and seasonal vaccination approaches. There is no evidence to date showing that one vaccine performs better than the other. Go to footnote 8
- 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
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).
- Go back to footnote reference 4
Datoo MS, Dicko A, Tinto H, Ouédraogo JB, Hamaluba M et al. Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial. Lancet. 2024;403(10426):533–544. doi:10.1016/S0140-6736(23)02511-4
- Go back to footnote reference 5
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 20 May 2026).
- Go back to footnote reference 6
Mwapasa V, Asante KP, Milligan P, Akech S, Oduro A et al. Impact of introducing the RTS,S/AS01E malaria vaccine on mortality in young children in Ghana, Kenya, and Malawi: an observational evaluation of a cluster randomised implementation programme. Lancet. 2026;407(10541):1796–1808. doi:10.1016/S0140-6736(26)00248-5.
- Go back to footnote reference 7
Chandramohan D, Zongo I, Sagara I, Cairns M, Yerbanga RS et al. Seasonal malaria vaccination with or without seasonal malaria chemoprevention. N Engl J Med. 2021;385(11):1005–1017. doi:10.1056/NEJMoa2026330.
- Go back to footnote reference 8
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).
