Despite decades of research, scientists have so far been unable to develop a fully effective vaccine for malaria. Now, a new vaccine candidate is showing real promise for children in Africa. With recent Phase II results demonstrating an efficacy of 77%, the vaccine could save millions of lives – if it holds up in further clinical trials. But why is it so hard to develop a malaria vaccine, and what sets this new one apart from previous attempts?
By Amy LeBlanc. Header Image: Twins Dorcas and Deborah Bendak, 7, under their old mosquito net at their home in Musoma. They both received a new mosquito net at Iringo B primary school. Credit: Riccardo Gangale/VectorWorks, Courtesy of Photoshare
Nearly half of the world’s population is at risk of malaria, a disease caused by plasmodium parasites transmitted by certain types of mosquitoes. In 2019, the World Health Organization (WHO) estimated there were a total of 229 million cases around the world, with an annual death toll of over 400,000. The most vulnerable group is tragically children, with African children under the age of five accounting for a horrific two-thirds of global malaria deaths every year.
Prof. Anna Rosanas-Urgell is Head of the Malariology Unit at the Institute of Tropical Medicine in Antwerp. She explained that malaria is currently being combatted using a range of methods, but that we’re desperately in need of new solutions:
“As with any disease, the Holy Grail will be to have a vaccine that works in more than 90% of cases. But for the moment, we don’t have a bulletproof solution to malaria. Instead, we are using a toolbox of approaches: every year, billions of dollars are spent on preventative measures such as bed nets, insecticide spraying, and antimalarial drugs.”
“Over the past 15 years, these tools have led to a significant decrease in global malaria cases. However, in the last 2-3 years, this decrease has stalled; despite our best efforts, malaria is even on the rise again in some regions. There are multiple factors contributing to these worrying trends, including increased drug resistance in Asia and disturbance of control strategies or a lack of surveillance in certain African countries. To be able to tackle this disease effectively, we really need new tools. Especially vaccines.”
Why is it so hard to develop an effective malaria vaccine?
With the speed of COVID-19 vaccine development, it may be hard to comprehend why there isn’t already a malaria vaccine available. Indeed, the idea of a malaria vaccine has been around for a long time, and over 140 malaria vaccine candidates have already been tested in humans. To date, only one vaccine has been approved for pilot use: Mosquirix, by GlaxoSmithKline (GSK), with an efficacy of 30%. This is well below the 75% target set by the WHO.
“As with any disease, the Holy Grail will be to have a vaccine that works in more than 90% of cases.” – Anna Rosanas-Urgell, ITM
The reasons for the slow progress are about as complicated as the malaria plasmodium’s lifecycle. These parasites have plagued humans for over 30 million years, changing over time in an evolutionary arms race against our immune systems. The resulting creatures are complex, with multi-stage lifecycles and more than 5,000 genes as potential vaccine targets. By comparison, the COVID-19 virus has just 12 genes and an obvious spike protein for vaccine designers to target.
In addition to the technical complexities, malaria also suffers from a lack of prioritization that is common to many tropical diseases, according to Rosanas-Urgell:
“Funding in research is always limited. Tropical diseases affect poor populations in the most vulnerable places in the world, and many are neglected by pharmaceutical companies. This is because vaccine development for these diseases is often more challenging, but also because they have a lower profit margin. For a tropical disease, malaria has actually received a comparably large amount of attention over the past few years, largely due to a dedicated WHO campaign to control and eradicate it. But we still have a long way to go.”
Effective and affordable: grand hopes for a new vaccine
Thankfully, an effective malaria vaccine could now be closer than ever before. An international team of researchers recently announced the results of a Phase II trial in Burkina Faso, where a new malaria vaccine called R21 demonstrated an efficacy of 77% when given to 450 children. It’s a landmark achievement, says Rosanas-Urgell:
“This is the first malaria vaccine to have shown an efficacy above the recommended WHO level of 75%, which is fantastic! But the vaccine is not yet comparable with previous efforts at vaccine development, such as the GSK vaccine, because it still needs to go through Phase III. It is very promising,: the adjuvant in this vaccine is different from the one used in Mosquirix, and R21 uses more modern production methods, meaning that it would be cheaper and could easily be produced at large scale.”
“Although we need to wait for the Phase III results, there in room for hope. In the meanwhile, we will continue to work hard on other tools for the toolbox.” – Anna Rosanas-Urgell, ITM
The Phase III trial for the new vaccine is now underway with a larger number of children in four different African countries. The vaccine is truly a global effort, with the design and early development done at the University of Oxford, the adjuvant provided by US/Swedish biotech Novavax, and the manufacturing done by the world’s largest vaccine supplier, the Serum Institute of India. If the Phase III trial goes well, the vaccine could be approved and rolled out as early as 2023.
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“Although we need to wait for the Phase III results, there in room for hope,” says Rosanas-Urgell. “In the meanwhile, we will continue to work hard on other tools for the toolbox. To control and eliminate tropical diseases we really need a combination of things: we need more research and innovation; we need solid surveillance systems; we need leadership to establish concrete goals and strategies; but we also really need global development. As soon as countries experience economic growth, the nutrition, sanitation, and overall health of the population increases. With development, tropical diseases decline.”
