Two promising malaria vaccines: What comes next?

Long considered the holy grail of tropical medicine, malaria vaccines have been in development for more than 50 years. Dozens of candidates are currently in development, and two – the RTS,S/AS01 (RTS,S) and R21/Matrix-M (R21) – are on the cusp of large-scale deployment. A massive global effort is underway to scale up supply and ensure these vaccines reach those most vulnerable.  

While neither is considered the ‘silver bullet’ solution to end malaria, both show tremendous promise as complementary prevention tools that can save tens of thousands of lives annually if administered at full scale. That’s a big if: demand is estimated at 80-100 million children annually, and the cost of procurement and delivery is currently much higher than existing interventions.

The stakes are enormous: Nearly half a million children die every year from this mosquito-borne disease. Progress in reducing mortality has stalled in recent years, due in part to emerging drug and insecticide resistance that have rendered existing tools less effective.  

The dawn of a new era: from pilots to large-scale deployment 

Developing a high-efficacy malaria vaccine has proven incredibly difficult due to the multi-stage lifecycle of malaria parasites and their ability to evade immune system detection. In 2021, RTS,S became the first-ever malaria vaccine to receive World Health Organization (WHO) approval for widespread use. Developed by GSK, RTS,S has already been administered to nearly 1.5 million children through pilots in Kenya, Ghana, and Malawi. The 4-dose vaccine has shown to reduce malaria cases by 40% among young children after four years of follow-up. Another study found that RTS,S is 75% effective in preventing malaria when administered before the rainy season in highly seasonal transmission areas (I.e. West Africa, Sahel region). These rates of efficacy are not insignificant: researchers estimate RTS,S can save 24,000 lives for every 30 million doses administered.  

Mothers and children at the RTS,S vaccine roll-out in Homa Bay, Kenya. Photo courtesy of WHO.

On the heels of RTS,S is the University of Oxford’s R21 vaccine. A recent Phase 2 trial in 450 children living in a seasonal malaria transmission area of Burkina Faso showed that R21 was 77% effective in preventing severe malaria among young children, with protection lasting at least 12 months. Now R21 faces a greater test: an ongoing Phase 3 trial has enrolled 4,800 children in numerous East and West African countries of both seasonal and year-round transmission. Phase 3 trial data will be released later this year; and if the data continues to show high levels of efficacy and safety, that will likely set the stage for WHO approval.  

In the meantime, Ghana and Nigeria have granted provisional approval of R21. Nigeria’s approval is particularly significant: the country accounted for 38.4% of global malaria deaths among young children in 2021.

Global partnerships emerge to meet surging demand 

Gavi, the Vaccine Alliance, has invested over $150 million in the deployment of RTS,S, and has established a funding agreement with GSK and MedAccess to ensure the delivery of 18 million doses by 2025. These doses have already been allocated to 12 African countries, including the pilot countries Kenya, Ghana, and Malawi. UNICEF is the primary buyer and will work with countries to supply these doses largely through existing national immunization programs, creating a pathway to reach millions of the most at-risk children.   

Countries across Africa have applied for funding and support to rollout of the new vaccine. Since demand far exceeds supply, countries will work with Gavi to prioritize the most vulnerable and high-risk populations, such as children with limited access to malaria prevention services or who live in dense, high-transmission areas. Beyond 2025, RTS,S production is expected to increase to 15 million doses per year thanks to a product transfer deal with Bharat Biotech, of Hyderabad, India. 

Gavi also stands ready to fund the roll-out of R21 once approved by the WHO. R21’s manufacturer, Serum Institute of India Pvt Ltd (SII), has already committed to producing 100-200 million doses annually once the WHO recommendation is made. In addition, SII recently completed a technology transfer deal to produce the vaccine in Ghana, upon the completion of a factory in Accra.

National funding and community awareness vital to long-term success 

Vaccine procurement and delivery are relatively expensive – RTS,S ranges from $25 to $37 per fully vaccinated child – compared to mosquito nets and other prevention tools. While global donors like Gavi are supplementing costs during this roll-out phase, countries must find sustainable funding sources to cover the considerable ongoing costs, including procurement of vaccines and supplies, cold-chain distribution and storage costs (malaria vaccines must be shipped and stored at freezing cold temperatures),  community-level training, and communications efforts to promote the vaccine.   

A health official monitors the temperature of an ultra-cold chain freezer storing mRNA COVID-19 vaccines at ultra-low temperatures in Zambia. The R21 and RTS,S malaria vaccines both need to be shipped and stored at freezing cold temperatures. Photo courtesy of UNICEF.

Educating parents about the safety and benefits of these new products is a key driver of success for malaria vaccine programs. Social behavioral change communications must stress the importance of receiving every dose to maximize the effectiveness of the vaccine. Results from the RTS,S pilot revealed that 34% of participating children did not complete the 4-dose course. 

A promising pipeline of new vaccine candidates   

Dozens of malaria vaccine candidates are currently in development; and the vast majority are at the discovery, pre-clinical or phase 1 trial stage. With over 25 million babies born in malaria-endemic African countries every year, this pipeline of candidates will hopefully generate a robust marketplace of high-efficacy malaria vaccines – a market that prioritizes reaching the most at-risk over profits.  

 As we commemorate the Day of the African Child, United to Beat Malaria and Shot@Life applaud the remarkable progress made by the malaria vaccine community, helping accelerate Africa’s Agenda for Children 2040 by “fostering an Africa fit for children,” where every child can survive and have a healthy childhood. 

Note: This post has been updated to reflect the allocation of the first 18 million doses of the RTS,S vaccine.