Malaria vaccines (RTS,S and R21)

Despite progress, efforts to control malaria face many challenges. There were an estimated 263 million new malaria cases and 597 000 malaria deaths globally in 2023. The WHO African Region continues to shoulder the heaviest malaria burden, comprising 94% of malaria cases and 95% of malaria deaths globally.

Children are particularly vulnerable;  WHO estimates that about 432 000 African children died from malaria in 2023.

WHO updated their recommendation for malaria vaccines in October 2023.  The updated recommendation is applicable to both RTS,S/AS01 and R21/Matrix-M malaria vaccines:

WHO recommends the use of malaria vaccines for the prevention of P. falciparum malaria in children living in malaria endemic areas, prioritizing areas of moderate and high transmission.

• The malaria vaccine should be provided in a schedule of 4 doses in children from around 5 months of age. (Vaccination programmes may choose to give the first dose at a later or slightly earlier age based on operational considerations.)
• A 5th dose, given one year after dose 4, may be considered in areas of highly seasonal transmission or where malaria risk remains high during the third year of life or beyond.
• In areas with highly seasonal malaria transmission or areas with perennial malaria transmission with seasonal peaks, countries may consider providing the vaccine using an age-based administration, seasonal administration, or a hybrid of these approaches.
• Countries should prioritize vaccination in areas of moderate and high transmission but may also consider providing the vaccine in low transmission settings. Decisions on expanding to low transmission settings should be considered at a country level, based on the overall malaria control strategy, cost-effectiveness, affordability, and programmatic considerations.
• Malaria vaccines should be provided as part of a comprehensive malaria control strategy.

As of October 2023, both the RTS,S/AS01 and R21/Matrix-M vaccines are recommended by WHO to prevent malaria in children. Malaria vaccines should be provided to children in a schedule of 4 doses from around 5 months of age. Vaccination programmes may choose to give the first dose at a later or slightly earlier age based on operational considerations.

The malaria vaccines act against P. falciparum, the deadliest malaria parasite globally and the most prevalent in Africa.

The RTS,S malaria vaccine was first recommended by WHO to prevent malaria in children in October 2021. The vaccine reached more than 2 million children in Ghana, Kenya and Malawi through the Malaria Vaccine Implementation Programme (MVIP) from 2019 to 2023. Independent evaluations of the pilot introductions of the RTS,S vaccine in these 3 countries demonstrated high public health impact: a vaccine-attributable 13% drop in mortality among children age-eligible for vaccination; substantial reduction in hospitalizations for severe malaria; and, improved access to at least one malaria prevention intervention (malaria vaccine or insecticide treated net), reaching more than 90% of children. The pilot programme was completed at the end of 2023 and all countries are continuing their malaria vaccination programmes.

Both malaria vaccines are safe and efficacious, and both have been prequalified by WHO. In phase 3 clinical trials both vaccines reduced malaria cases by more than half during the first year after vaccination – the period when children are at high risk of illness and death. A fourth vaccine dose given in the second year of life prolonged protection. Both vaccines reduce malaria cases by 75% when given seasonally in areas of highly seasonal transmission where seasonal malaria chemoprevention is provided.

Highest impact is achieved when a combination of WHO-recommended preventive, diagnostic, and treatment strategies are used, tailored by the country to the local context. Roll out of malaria vaccines is well underway. By early April 2025, 19 countries had introduced the vaccine sub-nationally as part of routine childhood vaccinations, with scale-up and additional roll-outs planned throughout the year. Tens of thousands of young lives could be saved every year with scale up of these malaria vaccines.

Both the R21 and RTS,S vaccines are shown to be safe and effective in preventing malaria in children and are expected to have high public health impact.

RTS,S has been shown in large pilot implementations to substantially reduce malaria illness and deaths in young children. Given the similarity of the two malaria vaccines, it is likely that R21 will also be highly impactful. Tens of thousands of young lives could be saved every year with the wide implementation of these malaria vaccines.

The R21 and RTS,S malaria vaccines have not been tested in a head to head trial. Both have been shown to reduce malaria cases by more than half during the first year after vaccination – this is the period when children are at highest risk of malaria illness and death. A fourth dose prolongs the protection. Both vaccines prevent around 75% of malaria episodes when given seasonally in areas of highly seasonal transmission where seasonal malaria chemoprevention is provided.

There is no evidence to date showing one vaccine performs better than the other.

The choice of product to be used in a country should be based on programmatic characteristics, vaccine supply and vaccine affordability. Gavi, the Vaccine Alliance, has established an exceptional time limited co-financing policy for malaria vaccines, to increase affordability. Many Gavi-supported countries will pay as little as US$ 0.20 per dose for either vaccine.

Multiple modelling studies show cost-effectiveness of malaria vaccines according to standard measures. R21, which is currently less expensive than RTS,S, is estimated to have similar cost effectiveness to other malaria control interventions, and both malaria vaccines are estimated to be highly cost-effective when compared with other childhood vaccines. Costing studies show malaria vaccine introduction costs are similar to the costs of other new vaccines at introduction.

The RTS,S vaccine was prequalified by WHO in July 2022. The R21 malaria vaccine was prequalified by WHO in December 2023. WHO prequalification ensures vaccine safety and quality.

Rollout of the RTS,S and R21 malaria vaccines is well underway. By early April 2025, 19 countries in Africa (Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Côte d’Ivoire, Chad, Democratic Republic of the Congo, Ghana, Kenya, Liberia, Malawi, Mozambique, Niger, Nigeria, Sierra Leone, South Sudan, Sudan and Uganda) were offering malaria vaccines as part of their childhood immunization programmes, and according to their national malaria control plans. Additional countries are expected to introduce and scale up either RTS,S or R21 malaria vaccines in 2025. The status of introduction can be found on the malaria vaccine introduction dashboard.

Demand for the malaria vaccines is unprecedented. At least 30 countries in Africa plan to introduce the malaria vaccine into their childhood immunization programmes and as part of their national malaria control strategies.

With two malaria vaccines recommended and available, vaccine supply is expected to be sufficient to meet the high demand.

The availability of two safe and effective malaria vaccines, RTS,S and R21, results in sufficient vaccine supply to meet demand and benefit children living in areas where malaria is a major public health risk.

Tens of thousands of young lives could be saved every year with the wide implementation of these malaria vaccines. According to modelling estimates, malaria vaccines could prevent approximately half a million child deaths by 2035 if they were scaled up in moderate and high malaria transmission areas.

The Malaria Vaccine Implementation Programme (MVIP) in Ghana, Kenya and Malawi was completed at the end of 2023. All 3 countries continued provision of malaria vaccination through the childhood immunization programme with Gavi support

The MVIP was designed to evaluate the public health use of the RTS,S vaccine in Ghana, Kenya and Malawi. Between 2019 and 2023, more than 2 million children were reached with the malaria vaccine across the 3 countries, and implementation resulted in a substantial drop in mortality (13%) among children age-eligible for the vaccine, as well as a reduction in hospitalizations for severe malaria.

The success of the MVIP and lessons learned through the pilot programme informed R21 vaccine considerations and facilitated more efficient development of additional malaria vaccines, including the WHO recommendation for the second malaria vaccine, R21.

The MVIP was coordinated by WHO and supported by in-country and international partners, including Ministries of Health in Ghana, Kenya and Malawi, PATH, UNICEF and GSK. Financing for the MVIP was provided by Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and Unitaid.