According to Gavi, the global vaccine alliance, 25 African countries had incorporated malaria vaccines into routine immunization programs by late January 2026, with more than 39 million doses delivered by that date. Zambia's government officially introduced the R21/Matrix-M vaccine into its national immunization program on October 27, 2025, aiming to vaccinate over 500,000 children aged 6 to 8 months.
The path began two years earlier. On October 2, 2023, the World Health Organization recommended R21/Matrix-M as the second WHO-approved malaria vaccine for children, following RTS,S/AS01, which received WHO endorsement in 2021. The recommendation followed consultations with WHO expert groups SAGE and MPAG, confirmed by WHO Director-General Tedros Adhanom Ghebreyesus. Malaria, transmitted by mosquitoes, kills approximately one child in Africa every minute, making it a leading cause of childhood death across the continent.
Demand for the first vaccine, RTS,S, far exceeds supply, making the second vaccine essential to protect more children faster and move toward a malaria-free future, said WHO Director-General Tedros. According to WHO Regional Director for Africa Matshidiso Moeti, the new vaccine offers real potential to close the supply-demand gap and could save hundreds of thousands of young lives when deployed at scale.
Clinical trial efficacy
In areas with highly seasonal malaria transmission—where transmission occurs mainly during four to five months of the year—the vaccine reduced symptomatic malaria cases in the twelve months following a three-dose series by 75 percent. A fourth dose administered one year later maintained this protection. In an age-based dosing schedule, efficacy over the same period was 66 percent, with a fourth dose preserving protection. The WHO emphasizes that R21 has not been directly compared to RTS,S in a head-to-head trial, and no evidence yet shows one vaccine outperforms the other. At prices between 2 and 4 US dollars per dose, R21 offers cost-effectiveness comparable to other malaria interventions and childhood vaccines.
Phase 3 trial: 4,878 children received first dose
The recommendation rested largely on a Phase 3 trial published in The Lancet, conducted at five sites across four African countries with varying malaria transmission patterns. Between April 26, 2021 and January 12, 2022, researchers enrolled 5,477 children aged 5 to 36 months and randomly assigned 4,878 to receive either the vaccine or a licensed rabies vaccine as control in a 2:1 ratio. Vaccinations occurred as three doses four weeks apart, with a booster twelve months after the third dose. Twelve-month efficacy against clinical malaria reached 75 percent at seasonal sites and 68 percent at sites with year-round transmission. The Serum Institute of India, which manufactures the vaccine, co-funded the trial—a conflict of interest the publication discloses.
Safety review: a mortality signal, causation unclear
The WHO Global Advisory Committee on Vaccine Safety updated its assessment at a November 13-15, 2023 meeting, published March 1, 2024 in the WHO Weekly Epidemiological Record. The trial reported 142 serious adverse events total, balanced between vaccine and control groups. Six met the threshold for vaccine-relatedness, all febrile seizures. The febrile seizure risk fell within the range observed with other vaccines, and all cases resolved without lasting effects. The committee noted an imbalance in deaths: 15 in the vaccine group versus 4 in the control group. Excluding deaths from injuries, the count was 12 versus 3. The difference was not statistically significant, though the committee acknowledged limited statistical power for this endpoint. No temporal pattern emerged relative to vaccination timing or cause of death. Among factors including seasonal malaria chemoprevention, bed net use, and nutritional status, none explained the imbalance, and the vaccine worked equally in underweight children. The committee noted that few young children worldwide had received the Matrix-M adjuvant compared to adults. It concluded no serious safety concerns warranted delaying recommendation but advised close monitoring during rollout, including for febrile seizures, mortality, and severe malaria.
Comparing the two malaria vaccines
R21/Matrix-M is not the first malaria vaccine. Beginning in 2019, Ghana, Kenya, and Malawi launched a WHO-coordinated pilot program with RTS,S/AS01. Nearly 2 million children have been reached there since, and the pilot reduced severe malaria, hospitalizations, and child deaths substantially. Those three countries now operate under the regular Gavi malaria immunization program, with board funding approved in December 2021 for 2022-2025. The scale of the problem explains the urgency: Africa accounts for 94 percent of global malaria cases and 95 percent of deaths worldwide. Children under five represent over 75 percent of all malaria deaths globally. In 2023 alone, malaria caused 597,000 deaths worldwide, including 432,000 in African children. According to WHO estimates, the vaccine saves one life per 200 vaccinated children.
Surveillance gaps in rollout
The safety committee recommended a strongly coordinated approach to monitoring during full rollout but noted a critical constraint: most countries receiving the vaccine are low- and middle-income nations with limited capacity for data collection, investigation, and causality assessment. The underlying trial continues through 2028 at three sites—Nanoro and Bougouni in Burkina Faso and Dande in Burkina Faso—following children until school age. As of February 2026, no new participants were enrolled, with final completion projected for April 2028. Gavi has made continued support contingent on adequate financing.