A vaccine now exists for malaria, a parasitic disease spread through the bite of infected Anopheles mosquitoes. For decades, the complex life cycle of the Plasmodium falciparum parasite—the species responsible for most malaria deaths—presented a major challenge to vaccine development. The parasite’s ability to constantly change its form and hide from the human immune system across different stages made development difficult. After extensive research, the World Health Organization (WHO) formally recommended the first malaria vaccine for use in children living in regions with moderate to high malaria transmission. This advancement is crucial in the fight against a disease that causes hundreds of thousands of deaths globally each year, mostly in young children.
The First Approved Vaccine
The first approved vaccine is known scientifically as RTS,S/AS01, marketed under the brand name Mosquirix. This recombinant protein-based vaccine was developed by GlaxoSmithKline (GSK) in partnership with the PATH Malaria Vaccine Initiative. Following clinical trials, the European Medicines Agency (EMA) issued a positive scientific opinion. In October 2021, the WHO officially recommended its broader use, informed by a pilot program in Ghana, Kenya, and Malawi that demonstrated its feasibility and public health impact.
The RTS,S vaccine provides moderate but substantial protection in high-risk areas. In children aged 5 to 17 months who received four doses, the vaccine prevented approximately 36% of clinical malaria cases over four years. Pilot programs showed the vaccine was associated with a 13% drop in deaths from all causes among eligible children and a 22% reduction in severe malaria hospitalizations. It is currently recommended for children from five months of age in a four-dose schedule, integrating into routine childhood immunization programs.
Targeting the Parasite Life Cycle
Developing a malaria vaccine proved difficult because the Plasmodium falciparum parasite undergoes multiple transformations within the human host and the mosquito vector. When an infected mosquito bites a human, it injects sporozoites into the bloodstream, which quickly travel to the liver. Inside the liver cells, the parasite replicates massively in a stage called pre-erythrocytic schizogony, releasing thousands of merozoites into the bloodstream. These merozoites invade red blood cells, beginning the blood stage that causes symptomatic illness, severe disease, and death.
The RTS,S vaccine targets the parasite during the initial, pre-erythrocytic stage, before it multiplies in the liver and causes disease. The vaccine trains the immune system to recognize the Circumsporozoite Protein (CSP), the most abundant protein found on the surface of the sporozoite. By generating antibodies against the CSP, the vaccine aims to neutralize sporozoites in the blood or prevent them from successfully invading liver cells. Blocking the parasite at this stage prevents the massive multiplication that initiates the symptomatic blood-stage infection.
Global Implementation and Access
The rollout of the RTS,S vaccine has focused on Sub-Saharan Africa, where the burden of Plasmodium falciparum malaria is heaviest. Initial deployment was managed through the Malaria Vaccine Implementation Programme (MVIP), running pilot programs in high-transmission areas of Ghana, Kenya, and Malawi. These pilots assessed the feasibility of delivering the vaccine through existing routine childhood immunization schedules, which require a complex cold chain and multi-dose scheduling. The studies confirmed that delivering a four-dose regimen was manageable and widely accepted by communities.
Global health organizations, including the WHO and Gavi, the Vaccine Alliance, fund and coordinate the broader deployment. Gavi approved funding to support the introduction of the vaccine into national immunization programs. However, the initial supply of RTS,S from GSK was limited, necessitating a framework to allocate available doses to areas of highest need. This coordination helps overcome logistical hurdles, such as ensuring a consistent cold chain for transport and training health workers for the multi-dose schedule.
Next Generation Vaccine Candidates
While RTS,S represents a breakthrough, research continues to develop vaccines with higher efficacy and greater scalability. The most prominent next-generation candidate is the R21/Matrix-M vaccine, co-developed by the University of Oxford and the Serum Institute of India. Like RTS,S, this newer vaccine targets the Circumsporozoite Protein, but it uses a different structure and adjuvant—a substance added to enhance the immune response.
R21/Matrix-M has shown promising results in Phase 3 trials, demonstrating an average efficacy of 78% over the first year in children aged 5 to 17 months. This efficacy exceeds the WHO’s 75% target and led to the WHO’s recommendation for its use in October 2023, making it the second approved malaria vaccine. The Serum Institute of India has established substantial manufacturing capacity, planning to produce up to 200 million doses annually to meet global demand. Other novel approaches, such as whole sporozoite vaccines that use weakened or irradiated parasites, are in earlier phases of development, aiming to induce a broader immune response against multiple parasite antigens.