Malaria kills hundreds of thousands of people each year, mostly children under the age of five living in Africa. While there are treatments for the disease that can help lessen its impact, stopping it entirely is a different challenge: It’s notoriously difficult to make a malaria vaccine that works well. When the latest attempt at abmalaria vaccine rolled out in 2019—after more than 30 years of development—it was only around 30% effective at preventing severe disease. But could the mRNA technology used to make COVID vaccines help?
“The technology allows us to deal with the complexity of malaria,” says Uğur Şahin, CEO and cofounder of BioNTech, the German company that worked with Pfizer to create the first approved COVID-19 vaccine—which was also the first mRNA vaccine ever on the market. As the company continues to work on new versions of the COVID vaccine, it’s now also embarking on an mRNA vaccine for malaria.
The company was already working on vaccines and immunotherapy treatments for HIV and tuberculosis—two other diseases that disproportionately affect poorer countries—through grants from the Gates Foundation. It wanted to work on malaria in the past. But because malaria vaccines are particularly complex, it needed more funding. Now, with the success of the COVID vaccine, it has the resources to invest.
Malaria is “really a complex pathogen,” Şahin says. “It is a huge pathogen with a large genome. It has multiple mechanisms to enter fast and to hack the immune system, and it requires a lot of resources.” The virus that causes COVID, by contrast, is relatively simple to target. Malaria isn’t a virus or a bacteria; it’s caused by a parasite called Plasmodium, which has a complex life cycle that goes back and forth between the blood in infected humans and mosquitoes. The parasites change throughout their lifecycle, so they’re difficult to target. They also secrete a protein that blocks the immune system from creating memory T cells, part of the system that the body uses to recognize a disease it has encountered before.
The new vaccine may attack the pathogen in several ways, something that’s possible with an mRNA vaccine. “The immunology of malaria is that malaria uses multiple pathways to overcome the immune recognition, and it’s quite possible that the vaccine has to deliver not only a single antigen, but several antigens,” he says. In previous work on cancer treatments, the company used mRNA to deliver as many as 20 different antigens with one injection. mRNA can also “precisely engineer the immune response,” he says, and it will let the company quickly develop 20-plus different vaccine candidates simultaneously, something that couldn’t easily happen with more traditional vaccines.
The company plans to partner with experts who have spent decades studying malaria. Other groups are also using mRNA to develop new malaria vaccines, including scientists from the University of Pennsylvania, the Walter Reed Army Institute of Research and Naval Medical Research Center, and Acuitas Therapeutics, who worked together to create a new vaccine that successfully protected against malaria in trials with mice. Researchers at Yale University have developed a slightly different self-replicating RNA vaccine (unlike mRNA, the vaccine creates copies of itself inside the body, so it can use a lower dose) that also worked well in mice. Scientists at Oxford University, meanwhile, worked with collaborators to create another vaccine that doesn’t use mRNA but has proven to be effective in trials. The world may be on the verge of finally addressing one of the diseases that kills the most people.
BioNTech plans to begin clinical trials of the vaccine by the end of 2022. When it goes into production, the company plans to work with partners in Africa to locally manufacture the vaccine, potentially using the same mRNA factories that are being built now to make COVID vaccines. “Our ultimate aim is to transfer the technology to the people in Africa to work together with the African Centers of Disease Control, to work together with the WHO to use their training units,” Şahin says. The company also plans to digitize the process so that it can monitor and assist the production in real-time as manufacturing happens.
Now that the mRNA has been proven to work in COVID, Şahin believes that it can help with many other diseases. “A door is open to a new world of pharmaceuticals,” he says. “And I really mean that. This is not just a fancy technology that can do some better treatment. It really would allow us to develop therapies using mechanisms that cannot be addressed by the existing drugs. We believe that we have now the chance to develop new type of treatments against diseases that you would say, ‘Okay, this disease, we are at the moment not able to address, because we don’t have the appropriate type of technology.’ And this is exciting.”