Q&A on RTS,S malaria vaccine

RTS,S/AS01 (RTS,S) is a vaccine that acts against Plasmodium falciparum, the deadliest malaria parasite globally and the most prevalent in Africa. The vaccine significantly reduces malaria and life-threatening severe malaria in children. If implemented broadly, the vaccine could save tens of thousands of lives each year. 

On 6 October 2021, WHO recommended widespread use of the RTS,S malaria vaccine.

The WHO recommendation is based on results from an ongoing malaria vaccine pilot programme in  Ghana, Kenya and Malawi that has reached more than 1 million children since 2019. To date, more than 3 million doses have been administered through routine immunization programmes. Community demand for the vaccine is strong and evidence shows it can effectively be delivered through the routine child immunization platform.

Vaccine introduction is led by Ministries of Health in areas of the 3 participating countries, with support from WHO and international and country-level partners, including PATH, GSK and UNICEF.

Key findings of the pilot programme informed the WHO recommendation for the RTS,S malaria vaccine based on data and insights generated from two years of vaccination in child health clinics in the 3 pilot countries.

The pilot introduction of the RTS,S malaria vaccine in Ghana, Kenya and Malawi through the routine child immunization services has resulted in high uptake of the vaccine and reaffirmed its favorable safety profile. The vaccine resulted in a significant reduction in life-threatening severe malaria and in pediatric hospitalization with malaria infection. 

Specific findings include:

• Feasible to deliver: Vaccine introduction is feasible, with good and equitable coverage of RTS,S seen through routine immunization systems.
  
  
• Reaching the unreached: RTS,S increases equity in access to malaria prevention.
  • Data from the pilot programme showed that more than two-thirds of children in the 3 countries who are not sleeping under a bednet are benefiting from the RTS,S vaccine.
  • Layering the tools results in over 90% of children benefiting from at least one preventive intervention (insecticide treated nets or the malaria vaccine).
    
• Strong safety profile: To date, more than 3 million doses of the vaccine have been administered in 3 African countries - the vaccine has a favorable safety profile. 
  
  
• No negative impact on uptake of bednets, other childhood vaccinations, or health seeking behavior for febrile illness. In areas where the vaccine has been introduced, there has been no decrease in the use of insecticide-treated nets, uptake of other childhood vaccinations or health seeking behavior for febrile illness.
  
  
• High impact in real-life childhood vaccination settings: substantial reduction in deadly severe malaria, even when introduced in areas where insecticide-treated nets are widely used and there is good access to diagnosis and treatment. After the vaccine was introduced there was a substantial drop in children being hospitalized and a drop in child deaths in the age group that is eligible to receive the vaccine. 
  
  
• Highly cost-effective: Modelling has shown that the vaccine is cost effective in areas of moderate to high malaria transmission.

Other recent RTS,S clinical evidence shows that strategic delivery of the vaccine just prior to the high malaria transmission season in areas where malaria is highly seasonal can optimize impact and markedly reduce mortality, especially when combined with other recommended malaria control interventions.

Based on the advice of two WHO global advisory bodies, one for immunization and the other for malaria, the Organization made this recommendation.

WHO recommends the RTS,S/AS01 malaria vaccine be used for the prevention of P. falciparum malaria in children living in regions with moderate to high transmission as defined by WHO.

RTS,S/AS01 malaria vaccine should be provided in a schedule of 4 doses in children from 5 months of age for the reduction of malaria disease and burden. 

Drawing from a growing body of evidence, countries may consider providing the RTS,S/AS01 vaccine seasonally, with a 5-dose strategy in areas with highly seasonal malaria or areas with perennial malaria transmission with seasonal peaks.   

When countries choose the seasonal deployment of the RTS,S/AS01 vaccine, they are strongly encouraged to document their experience, including the vaccine effectiveness, feasibility and occurrence of any adverse events, to feed into future guidance updates. In addition, WHO encourages international and national funders to support relevant learning agendas.

RTS,S/AS01 introduction should be considered in the context of comprehensive national malaria control plans. 

A key next step for the WHO-recommended malaria vaccine was achieved when the Gavi Board on 2 December 2021 approved an investment to support malaria vaccine introduction, procurement and delivery for Gavi-eligible countries in sub-Saharan Africa in 2022-2025. An initial investment of US$ 155.7 million for 2022-2025 will initiate the implementation of this additional tool to “help drive down child mortality in Africa,” according to Gavi. 

Additional next steps for use of the malaria vaccine include country decision-making on whether to adopt the vaccine as part of national malaria control strategies.

WHO advises countries to move away from a “one-size fits all” approach and apply a mix of tools, tailored to local contexts, for maximum benefit. A malaria vaccine is a breakthrough addition to the malaria toolkit and can help get malaria control back on track.

Despite considerable progress with the scale up of insecticide treated nets (ITNs), deployment of chemoprevention approaches, and the adoption of highly effective treatment since 2000, malaria remains a primary cause of childhood illness and death in sub-Saharan Africa – and the situation is worsening. According to WHO’s latest data (World Malaria Report 2021) there were marked increases in malaria cases and deaths in 2020.

About 479 000 African children under the age of 5 died of malaria in 2020 – representing about 80% of malaria deaths in the African region. Globally, approximately 95% of cases and 96% of deaths were in sub-Saharan Africa. 

The WHO recommendation for wider use of the RTS,S malaria vaccine comes at a time when WHO and partners have called for new tools, including malaria vaccines, to help get malaria control efforts back on track. The addition of the RTS,S malaria vaccine to currently recommended malaria control interventions could save tens of thousands of lives annually and drive down child mortality in Africa.

When used in combination with existing prevention measures, RTS,S will accelerate the pace of malaria progress in Africa, improve child health and save lives.

In January 2016, the vaccine was recommended by WHO for pilot introduction in selected areas of the 3 African countries – Ghana, Kenya and Malawi – to learn more about the public health value of the vaccine in real-life routine immunization settings.

The WHO-coordinated malaria vaccine pilot programme was designed to address several outstanding questions related to the public health use of RTS,S – specifically, to assess: the feasibility of administering the recommended 4 doses of the vaccine; the vaccine’s role in reducing childhood deaths; and, its safety in the context of routine use.

Ministries of Health in the 3 pilot countries lead the malaria vaccine pilots. A consortium of in-country evaluation partners generated the data and evidence used to inform the WHO recommendation.

Pilot findings during the first two years of routine immunization affirm that the malaria vaccine is safe, feasible to deliver and reduces deadly severe malaria – after the vaccine was introduced there was a substantial drop in children being hospitalized and a drop in child deaths in the age group that is eligible to receive the vaccine.

More than 1 million vulnerable children have been reached with the malaria vaccine through the pilots so far, despite the context of COVID-19.  The resilience of the national immunization programmes to effectively deliver RTS,S has resulted in a significant reduction in severe malaria in the areas where the vaccine was deployed and provided additional malaria prevention for  young children. The WHO recommendation will ensure that many more children living in areas of moderate to high transmission can benefit from this life-saving intervention. 

The pilots will continue in the 3 pilot countries through 2023 to understand the added value of the 4^th vaccine dose, and to measure the longer-term impact on child deaths.

Ministries of Health of Ghana, Kenya and Malawi lead the pilots through each country’s routine immunization systems and will continue to do so.

The pilot programme is coordinated by WHO and supported by in-country and international partners, including PATH, UNICEF, and GSK, which is donating up to 10 million doses of the vaccine for the pilot.

Financing for the pilot programme has been mobilized through an unprecedented collaboration among three key global health funding bodies: Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and Unitaid.

The RTS,S malaria vaccine is the result of 30 years of research and development by GSK and through a partnership with PATH, with support from a network of African research centres. The Bill & Melinda Gates Foundation provided catalytic funding for late-stage development of RTS,S between 2001 and 2015.

RTS,S is the first and currently the only malaria vaccine that is recommended for use by WHO and received a positive scientific opinion from the European Medicines Agency (EMA), a stringent regulatory authority. It is the first malaria vaccine to be introduced by 3 Ministries of Health through their childhood immunization  programmes. More than 1 million children in Ghana, Kenya and Malawi have been vaccinated and are benefiting from the added protection provided by the vaccine as part of a pilot programme.

A second malaria vaccine could be highly beneficial to malaria control, particularly because it could increase supply to meet the anticipated high demand.