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) since 2019. Introduction of the RTS,S malaria vaccine in the 3 pilot countries resulted in a 13% drop in mortality among children age-eligible for vaccination and substantial reduction in hospitalizations for severe malaria. The pilot programme was completed at the end of 2023 and all 3 countries are continuing their vaccination programmes for the longer term. Wider implementation of malaria vaccines in additional countries will start in 2024.

Both malaria vaccines are safe and efficacious, and both have been prequalified by WHO. Given the similarity of the vaccines and that RTS,S has had substantial impact in areas of high, moderate and low transmission, it is likely that R21 will also be efficacious in all malaria endemic settings.

Tens of thousands of young lives could be saved every year with the wider implementation of these malaria vaccines. 

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

Given the similarity of the two malaria vaccines and that RTS,S has had substantial impact in areas of high, moderate and low transmission, it is likely that R21 will also be efficacious in all malaria endemic settings. 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 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. 

The RTS,S vaccine was prequalified by WHO in July 2022. The R21 malaria vaccine was prequalified by WHO in December 2023.

More than 2 million children in Ghana, Kenya and Malawi have already been vaccinated with the RTS,S malaria vaccine since 2019 through the WHO-coordinated Malaria Vaccine Implementation Programme (MVIP). Since the completion of the MVIP at the end of December 2023, the 3 countries will continue and expand their vaccination programmes with Gavi-supported vaccines.

A broader rollout of malaria vaccines is moving forward. In November 2023, the first shipment of RTS,S vaccine arrived in Cameroon, a country not previously involved in the malaria vaccine pilot programme, with additional deliveries to other countries continuing. Cameroon and additional countries plan to launch introduction of the malaria vaccine in early 2024.

Demand for the malaria vaccines is unprecedented. At least 28 countries in Africa plan to introduce the malaria vaccine into their childhood immunization programmes and as part of their national malaria control strategies.

Annually at least 40–60 million doses of malaria vaccine will be needed by 2026; growing to 80–100 million doses each year by 2030.

The addition of the second malaria vaccine (R21) to complement the ongoing rollout of the first malaria vaccine (RTS,S) is expected to result in sufficient vaccine supply to meet demand.

The addition of the second malaria vaccine (R21) to complement the ongoing rollout of the first malaria vaccine (RTS,S) is expected to 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 broad implementation of these malaria vaccines.

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.