Malaria vaccines (RTS,S and R21)

Despite progress, efforts to control malaria face many challenges. There were an estimated 249 million malaria cases and 608 000 malaria deaths globally in 2022. The WHO African Region continues to shoulder the heaviest malaria burden, comprising 94% of cases and 95% of deaths globally.

Children are particularly vulnerable; nearly half a million African children die from malaria every year.

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

WHO recommends the programmatic 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 where there is a significant malaria risk remaining in children a year after receiving dose 4.
• In areas with highly seasonal malaria 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.
• Vaccine introduction should be considered in the context of comprehensive national malaria control plans.
  
  

As of 2 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 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, 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, in areas where seasonal malaria chemoprevention is provided.

Roll out of malaria vaccines is well underway, with 8 African countries now introducing malaria vaccine as part of routine childhood vaccinations, and more planning to introduce this 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 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 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 malaria vaccines is well underway. As of 25 April 2024, eight countries in Africa (Benin, Burkina Faso, Cameroon, Ghana, Kenya, Liberia, Malawi and Sierra Leone) offer malaria vaccine as part of their childhood immunization programmes, and according to their national malaria control plans. At least 10 more countries are likely to introduce RTS,S and R21 malaria vaccines this year.

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.

To meet country demand, at least 40–60 million doses of malaria vaccine will be needed annually by 2026, growing to 80–100 million doses each year by 2030.

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

The rollout of the two malaria vaccines, RTS,S and R21, will result 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. Modelling estimates both vaccines prevent up to half a million child deaths over 12 years if the vaccine is scaled up to all Gavi-eligible countries.

The Malaria Vaccine Implementation Programme (MVIP) was completed at the end of 2023. The MVIP countries of Ghana, Kenya and Malawi will continue and expand their malaria vaccination programmes with Gavi support.

The MVIP was designed to evaluate the public health use of the RTS,S vaccine in Ghana, Kenya and Malawi. Since 2019, more than 2 million children have been 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, and reduction in severe malaria hospitalizations.

The success of the MVIP and lessons learned through the pilot program 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 PATH, UNICEF and GSK, and Ministries of Health in Ghana, Kenya and Malawi. Financing for the MVIP was provided by Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and Unitaid.