WHO recommends R21/Matrix-M vaccine for malaria prevention in updated advice on immunization

The World Health Organization (WHO) has recommended a new vaccine, R21/Matrix-M, for the prevention of malaria in children. The recommendation follows advice from the WHO: Strategic Advisory Group of Experts on Immunization (SAGE) and the Malaria Policy Advisory Group (MPAG) and was endorsed by the WHO Director-General following its regular biannual meeting held on 25-29 September. 

WHO also issued recommendations on the advice of SAGE for new vaccines for dengue and meningitis, along with immunization schedule and product recommendations for COVID-19.  WHO also issued key immunization programmatic recommendations on polio, IA2030 and recovering the immunization programme.

The R21 vaccine is the second malaria vaccine recommended by WHO, following the RTS,S/AS01 vaccine, which received a WHO recommendation in 2021. Both vaccines are shown to be safe and effective in preventing malaria in children and, when implemented broadly, are expected to have high public health impact. Malaria, a mosquito-borne disease, places a particularly high burden on children in the African Region, where nearly half a million children die from the disease each year.

Demand for malaria vaccines is unprecedented; however, available supply of RTS,S is limited.  The addition of R21 to the list of WHO-recommended malaria vaccines is expected to result in sufficient vaccine supply to benefit all children living in areas where malaria is a public health risk.  

“As a malaria researcher, I used to dream of the day we would have a safe and effective vaccine against malaria. Now we have two,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. “Demand for the RTS,S vaccine far exceeds supply, so this second vaccine is a vital additional tool to protect more children faster, and to bring us closer to our vision of a malaria-free future.”

Dr Matshidiso Moeti, WHO Regional Director for Africa, emphasized the importance of this recommendation for the continent, saying: “This second vaccine holds real potential to close the huge demand-and-supply gap. Delivered to scale and rolled out widely, the two vaccines can help bolster malaria prevention and control efforts and save hundreds of thousands of young lives in Africa from this deadly disease.”

Key features of the R21 malaria vaccine:  

The updated WHO malaria vaccine recommendation is informed by evidence from an ongoing R21 vaccine clinical trial and other studies, which showed:

• High efficacy when given just before the high transmission season: In areas with highly seasonal malaria transmission (where malaria transmission is largely limited to 4 or 5 months per year), the R21 vaccine was shown to reduce symptomatic cases of malaria by 75% during the 12 months following a 3-dose series. A fourth dose given a year after the third maintained efficacy. This high efficacy is similar to the efficacy demonstrated when RTS,S is given seasonally.  
• Good efficacy when given in an age-based schedule:  The vaccine showed good efficacy (66%) during the 12 months following the first 3 doses. A fourth dose a year after the third maintained efficacy.  
• High impact: Mathematical modelling estimates indicate the public health impact of the R21 vaccine is expected to be high in a wide range of malaria transmission settings, including low transmission settings. 
• Cost effectiveness: At prices of US$ 2 – US$ 4 per dose, the cost-effectiveness of the R21 vaccine would be comparable with other recommended malaria interventions and other childhood vaccines. 
• Similarity of R21 and RTS,S vaccines: The two WHO-recommended vaccines, R21 and RTS,S, have not been tested in a head-to-head trial. 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
• Safety: The R21 vaccine was shown to be safe in clinical trials. As with other new vaccines, safety monitoring will continue.

Next steps for the second recommended malaria vaccine, R21/Matrix-M, include completing the ongoing WHO prequalification which would enable international procurement of the vaccine for broader rollout.

At least 28 countries in Africa plan to introduce a WHO-recommended malaria vaccine as part of their national immunization programmes. Gavi, the Vaccine Alliance has approved providing technical and financial support to roll out malaria vaccines to 18 countries. The RTS,S vaccine will be rolled out in some African countries in early 2024, and the R21 malaria vaccine is expected to become available to countries mid-2024. ;

Recommendations on dengue

• Dengue poses a significant public health burden in endemic countries and is poised to increase further both in terms of incidence and geographic expansion, due to climate change and urbanization.
• The live-attenuated quadrivalent dengue vaccine developed by Takeda (TAK-003) has demonstrated efficacy against all four serotypes of the virus in baseline seropositive children (4-16 years) in endemic countries and against serotypes 1 and 2 in baseline seronegative children.
• SAGE recommended that the vaccine be considered for introduction in settings with high dengue disease burden and high transmission intensity to maximize the public health impact and minimize any potential risk in seronegative persons.  
• SAGE recommended that the vaccine be introduced to children aged 6 to 16 years of age. Within this age range, the vaccine should be introduced about 1-2 years prior to the age-specific peak incidence of dengue-related hospitalizations. The vaccine should be administered in a 2-dose schedule with a 3-month interval between doses.
• SAGE recommended that vaccine introduction should be accompanied by a well-designed communication strategy and community engagement. 

Recommendations on meningitis

• SAGE recommended that all countries in the African meningitis belt introduce the novel pentavalent meningococcal conjugate vaccine targeting serogroups A, C, Y, W and X (Men5CV) into their routine immunization programmes in a single-dose schedule at 9 to 18 months of age.  
• In high-risk countries, and countries with high-risk districts, a catch-up campaign should also be conducted at the time of the introduction of Men5CV, targeting all individuals aged 1 to 19 years.  

  Recommendations on COVID-19

• SAGE was presented with updated data on the epidemiology of COVID-19, including death rates among priority-use groups; vaccine effectiveness data during Omicron XBB sub-lineages circulation; and pre-clinical and clinical data on novel monovalent XBB vaccines.
• Based on the data reviewed, SAGE recommended a simplified single-dose regime for primary immunization for most COVID-19 vaccines which would improve acceptance and uptake and provide adequate protection at a time when most people have had at least one prior infection.
• Available data suggest the monovalent Omicron XBB vaccines provide modestly enhanced protection compared to bivalent variant-containing vaccines and monovalent index virus vaccines. 
• When monovalent XBB vaccines are not available, any available WHO emergency-use listed or prequalified vaccine, bivalent variant-containing or monovalent index virus vaccines, may be used since they continue to provide benefits against severe disease in high-risk groups.

IA2030

• Progress against the IA2030 indicators was stalled due to the impact of the COVID-19 pandemic and was off-track for six of the seven impact goal targets; progress against the target for the introduction of new vaccines is on track driven by the introduction of new vaccines in low-income countries in 2022. 
• While there are promising signs of recovery, it is uneven; recovery is especially slow in low-income countries and vulnerable populations living in fragile and conflict-affected settings. 
• Low coverage of measles-containing vaccines has increased the risk of large, disruptive outbreaks. 
• A shared action agenda for 2023-2024 that sets out a series of short-term and high-level priorities to align the efforts of countries, regions, global partners, and other stakeholders has been developed. 
• The action agenda has six trajectories, which are catch-up and strengthening of immunization programmes, equity promotion, regaining control of measles, making the case for investment into immunization, accelerating the introduction of WHO-recommended vaccines, and advancing vaccination in adolescence.

The R21 and RTS,S vaccines act against P. falciparum, the deadliest malaria parasite and the most prevalent on the African continent. The updated WHO recommendation for malaria vaccines was informed by the results of the WHO-coordinated Malaria Vaccine Implementation Programme, through which nearly 2 million children in Ghana, Kenya and Malawi have been reached with the RTS,S/AS01 malaria vaccine since 2019. The pilot introduction of the first malaria vaccine has resulted in a substantial impact in reducing severe malaria illness, hospitalizations and child deaths. 

2 October 2023, WHO