A weapon against an ancient enemy that claims a child's life nearly every minute
Explore the BreakthroughsMalaria, a disease that has claimed millions of lives since ancient times, is finally facing a crucial blow. Still, nearly every minute a child dies from this infectious disease, which claimed an estimated 597,000 lives in 2023 5 . Young children are the most vulnerable; in that same year, an estimated 432,000 of the fatalities were children in the African Region 4 . For decades, scientists have grappled with the complex life cycle of the malaria parasite, which ingeniously evades our immune responses 1 . But now, after years of research, we are on the eve of a new era in malaria control. The advent of effective vaccines marks a turning point in a battle humanity has fought for so long.
The development of a malaria vaccine is one of the greatest challenges in modern medicine. Unlike viruses or bacteria, malaria is caused by a parasite of the genus Plasmodium, with Plasmodium falciparum being the deadliest variant 1 4 . This parasite has an exceptionally complex life cycle, using both humans and mosquitoes as hosts.
Throughout its life cycle, the parasite constantly changes form and composition, making it a moving target for our immune system 1 .
While most vaccines target one specific protein, an effective malaria vaccine must elicit a response against multiple stages of the parasite.
Yet development proved possible: both animal experimental research and the fact that people develop natural immunity after multiple infections showed that vaccination was feasible 1 .
A historic milestone was reached in 2021 when the World Health Organization (WHO) approved the first malaria vaccine, RTS,S 4 . Not long after, in 2023, a second vaccine, R21, followed 4 . Both vaccines target the pre-erythrocytic phase of the parasite - the stage before it leaves the liver and infects red blood cells.
The impact is significant: in large-scale implementation programs in Ghana, Kenya, and Malawi, administration of RTS,S led to a 13% decrease in mortality among children eligible for vaccination 4 . Both vaccines reduce malaria episodes by more than half in the first year after vaccination, and by about 75% in areas with highly seasonal transmission when combined with seasonal malaria chemoprevention 4 .
| Feature | RTS,S/AS01 | R21/Matrix-M |
|---|---|---|
| Recommended schedule | 4 doses from ~5 months | 4 doses from ~5 months |
| Effectiveness (Year 1) | >50% case reduction | >50% case reduction |
| Seasonal effectiveness | ~75% with SMC | ~75% with SMC |
| WHO prequalification | July 2022 | December 2023 |
Despite these successes, the first-generation vaccines are not perfect. Protection is limited in time, and effectiveness is well below that of most childhood vaccines 9 . The search for more powerful successors has therefore yielded a stream of innovation, with three promising approaches emerging.
A revolutionary approach comes from the Netherlands, where researchers from LUMC and Radboudumc developed a vaccine using genetically weakened malaria parasites 9 .
In the study, volunteers were exposed three times to mosquitoes carrying the genetically weakened GA2 parasite. They were then infected with a real malaria parasite. The results were remarkable: 8 out of 9 volunteers (89%) had developed good protection and did not get malaria 9 .
Australian researchers at WEHI chose a completely different approach: they developed a vaccine that does not prevent disease in humans but stops the spread of malaria via mosquitoes 2 .
Using advanced cryo-electron microscopy, they visualized a crucial protein complex essential for the fertilization of malaria parasites in the mosquito for the first time.
In preclinical studies, the vaccine triggered antibodies that blocked the transmission of malaria parasites to mosquitoes with an effectiveness of 99.7% 2 .
Sometimes nature itself provides the solution. Researchers at Radboudumc identified an extremely rare group of people whose blood can block the transmission of malaria parasites .
After screening hundreds of people, they discovered two individuals with exceptionally strong and long-lasting immunity: a Dutch missionary and a young girl from Uganda.
By isolating and studying the most powerful antibodies from their blood serum, the researchers identified the specific protein fragments these antibodies target. This information is now being used as a blueprint for developing a new vaccine against the spread of malaria .
| Approach | Mechanism of Action | Progress | Stated Advantage |
|---|---|---|---|
| Genetically weakened parasite (GA2) | Triggers natural immune response against whole parasite | Clinical study (phase 1b) | Breadth and duration of protection |
| Transmission-blocking (mRNA) | Blocks parasite fertilization in mosquito | Preclinical (promising) | Breaks transmission cycle |
| SUM-101 candidate | More effective protection in children | Clinical trial started in 2025 6 | Improved effectiveness in endemic areas |
Progress in malaria vaccine research has been made possible by a series of advanced research methods:
This technique allows researchers to visualize protein structures in atomic detail. It was crucial for imaging the fertilization complex of the malaria parasite and identifying vulnerable targets for vaccine development 2 .
By switching off specific genes in malaria parasites, researchers can create weakened parasites for vaccine purposes (such as GA2) or determine the function of specific proteins 9 .
This model, where volunteers are exposed to malaria parasites in a controlled manner under strict supervision, allows researchers to quickly and accurately test the efficacy of vaccine candidates 6 9 .
The same platform technology used for COVID-19 vaccines proves versatile. It allows researchers to quickly develop vaccines based on new targets, such as the transmission-blocking vaccine 2 .
| Research Reagent | Function in Vaccine Development |
|---|---|
| Genetically weakened GA2 parasite | Induces protective immune response without disease 9 |
| Recombinant Pfs230/Pfs48/45 proteins | Targets for transmission-blocking vaccines 2 |
| Monoclonal antibodies from immune donors | Identify natural immune response for replication |
| Matrix-M adjuvant (in R21) | Enhances immune response to the vaccine 4 |
| AS01 adjuvant (in RTS,S) | Improves vaccine effectiveness 4 |
The fight against malaria is not yet over, but the perspective has drastically changed. Where a quarter century ago an effective vaccine was still a distant dream, there are now two approved vaccines saving lives, and a pipeline full of innovative candidates promising even better protection 1 4 .
The challenges are still considerable - from logistical problems in remote areas to the complex four-dose schedules - but progress is undeniable 8 . Leading health organizations emphasize that the highest impact is achieved when vaccines are deployed as part of a combination of strategies, including bed nets, chemoprevention, and rapid diagnostics 3 4 .
On World Malaria Day 2025, WHO called for "Reinvest, Reimagine, Reignite" - a call to reinvest in proven interventions, reimagine strategies, and reignite our collective efforts 5 .
With continued investment, global collaboration, and the deployment of new generation vaccines, a world without malaria is getting closer. Science has provided the tools; now it is up to the global community to fully utilize them.