Malaria Vaccines RTS,S and R21: Global Rollout Progress 2026

What Are the WHO-Recommended Malaria Vaccines?

RTS,S/AS01 (brand name Mosquirix), developed by GSK in partnership with the PATH Malaria Vaccine Initiative over more than 30 years of research, became the world's first malaria vaccine to receive WHO recommendation in October 2021. The vaccine targets the circumsporozoite protein (CSP) on the surface of Plasmodium falciparum sporozoites — the form of the parasite injected by mosquitoes during a blood meal. RTS,S consists of the CSP antigen fused with hepatitis B surface antigen (HBsAg) and formulated with GSK's AS01 adjuvant system. The pivotal Phase III trial (conducted across 7 African countries in over 15,000 children) showed 36% efficacy against clinical malaria and 32% efficacy against severe malaria over 4 years of follow-up with a 4-dose regimen.

R21/Matrix-M, developed at the University of Oxford's Jenner Institute and manufactured by the Serum Institute of India, received WHO recommendation in October 2023. R21 uses a similar approach to RTS,S — targeting the CSP of P. falciparum — but with a higher proportion of the malaria antigen relative to the HBsAg carrier protein, combined with Novavax's Matrix-M saponin-based adjuvant. The Phase III trial, conducted in children aged 5-36 months in Burkina Faso, Mali, Kenya, and Tanzania, demonstrated 75% efficacy against clinical malaria over 12 months in areas with highly seasonal transmission (where children received vaccination just before the rainy season), and 68% efficacy in areas with perennial (year-round) transmission. A booster dose at 12 months maintained high efficacy into the second year.

Both vaccines are administered as a 4-dose series: three primary doses starting at approximately 5 months of age, given at monthly intervals, followed by a booster dose approximately 12 months after the third dose. The availability of two WHO-recommended vaccines is critically important for meeting the enormous demand — malaria kills approximately 600,000 people annually, the vast majority of whom are children under 5 in sub-Saharan Africa. With approximately 40 million children born each year in malaria-endemic areas of Africa, a single manufacturer could not produce enough doses to meet global need.

How Is the Global Vaccine Rollout Progressing?

The Malaria Vaccine Implementation Programme (MVIP), coordinated by WHO and funded by Gavi, Unitaid, and the Global Fund, piloted RTS,S in Ghana, Kenya, and Malawi beginning in 2019. Through these pilot programs, more than 2 million children received at least one dose of RTS,S, and over 13 million doses were administered by mid-2024. The real-world results were highly encouraging: childhood malaria deaths dropped by 13% in areas where the vaccine was introduced, and the vaccine was found to be safe, feasible to deliver through routine immunization programs, and reached children who were not sleeping under insecticide-treated bed nets — demonstrating that vaccination provides an additional, complementary layer of protection.

In 2023, Gavi's Board approved a landmark $160 million investment to support malaria vaccine rollout in eligible countries, with additional funding for subsequent years. More than 20 countries submitted applications for Gavi support, and by late 2025, vaccine introduction was underway or approved in countries including Cameroon, Burkina Faso, Sierra Leone, Liberia, Niger, Uganda, Benin, and the Democratic Republic of the Congo, among others. The Serum Institute of India's capacity to produce R21/Matrix-M at a cost of approximately $2-4 per dose (compared to approximately $10 per dose for RTS,S) is expected to dramatically expand the number of children who can be vaccinated.

Despite this progress, challenges remain. Supply constraints during the transition period (before R21 manufacturing reaches full capacity) mean that not all eligible countries can introduce the vaccine simultaneously. Integration into routine Expanded Programme on Immunization (EPI) schedules requires health worker training, cold chain capacity (RTS,S requires 2-8°C storage), community engagement to address vaccine hesitancy, and surveillance systems to monitor impact. The 4-dose regimen also presents logistical challenges, as maintaining high coverage through the booster dose requires strong follow-up systems. Initial data from the pilot programs showed that approximately 70% of children who received the first dose completed the full four-dose series — a coverage level that, while good, leaves room for improvement.

What Impact Could Malaria Vaccines Have on Global Health?

Mathematical models developed by Imperial College London and the WHO estimate that if malaria vaccination achieves high coverage across sub-Saharan Africa in conjunction with existing interventions (insecticide-treated bed nets, indoor residual spraying, seasonal malaria chemoprevention, and prompt diagnosis and treatment), it could prevent 40,000 to 80,000 childhood deaths annually and avert tens of millions of clinical malaria episodes. The exact impact depends on coverage levels, the number of doses received, the timing of vaccination relative to transmission seasons, and how the vaccine is integrated with other malaria control tools.

Importantly, malaria vaccines are not intended to replace existing interventions but to add a complementary layer of protection. Bed nets, which reduce malaria transmission by approximately 50%, remain essential. Seasonal malaria chemoprevention (SMC) — the periodic administration of antimalarial drugs to children during peak transmission season — has been shown to reduce clinical malaria by approximately 75% in areas with highly seasonal transmission. The MVIP pilot data demonstrated that RTS,S and bed nets together provided greater protection than either intervention alone, supporting an additive benefit model.

Looking ahead, next-generation malaria vaccines in development aim for even higher efficacy. Whole-sporozoite vaccines (such as PfSPZ Vaccine by Sanaria), which use radiation-attenuated live parasites, have shown up to 100% efficacy in controlled human malaria infection studies, though manufacturing scalability and cold chain requirements (-80°C storage) remain significant hurdles. mRNA-based malaria vaccine candidates, leveraging the platform technology proven during the COVID-19 pandemic, are in early clinical development by BioNTech and others. Transmission-blocking vaccines that target sexual-stage parasites could reduce community-level transmission even if they don't directly protect vaccinated individuals. The malaria vaccine field has been transformed from decades of frustration to a period of unprecedented optimism, though the path from clinical trials to global impact requires sustained investment, political commitment, and robust health system infrastructure.