Deaths from malaria, a life-threatening disease caused by Plasmodium parasites and spread by mosquitos, are especially high among African children. Now, two vaccines—RTS,S/AS01 and R21/Matrix-M—are recommended by the World Health Organization (WHO) to prevent malaria in children living in endemic areas of sub-Saharan Africa.
Research has shown that these vaccines, which target the P. falciparum malaria parasite, are safe and effective in preventing malaria in children, and alongside other prevention interventions, they are expected to make a significant public health impact. PATH partnered with GSK, WHO, and the ministries of health in Ghana, Kenya, and Malawi on the pilot implementation of RTS,S, which reached more than 2 million children between 2019 and 2023, and is a partner in the expanded rollout of malaria vaccines in additional sub-Saharan African countries.
Investigating synergies
While malaria vaccine efficacy in children is already firmly established, confirming similar efficacy in African adults is critical to determining whether vaccines like RTS,S can play a role in eliminating malaria in endemic countries. Research has found that putting two interventions together can provide stronger protection for children: studies combining RTS,S with antimalarial drugs in young African children showed a synergistic effect in averting clinical malaria infections.
To this end, PATH, in collaboration with the Kenya Medical Research Institute, Walter Reed Army Institute of Research, and GSK, conducted a Phase 2b study to test whether the clearance of pre-existing infections with antimalarial drugs could enhance overall malaria vaccine efficacy in adults living in malaria-endemic areas.
The study results showed that the level of vaccine efficacy seen in earlier studies with malaria-naïve adults in the United States was not achieved in Kenyan adults. The most unexpected and puzzling result was that the administration of antimalarial drugs—to clear ongoing infections assumed to blunt vaccine-induced immunity—did not substantively improve vaccine efficacy to the levels achieved in studies with US adults or an earlier study performed at the same Kenyan site where no drug treatment was given during the vaccination phase.
What the data tell us
This study highlights the importance of conducting vaccine trials in the populations who plan to use the vaccine. They also reaffirm the importance of testing hypothetical assumptions in well-designed clinical trials. More specifically, the results, published in The Journal of Infectious Diseases, offer critical insights to inform malaria vaccination strategies and future research regarding malaria vaccines for adults.
The findings do not diminish the proven efficacy of the vaccine in African children. Data from pilot evaluations in Ghana, Kenya, and Malawi have reaffirmed the impact of RTS,S and shown that malaria vaccines are saving lives in endemic regions, with a 13 percent reduction in all-cause mortality over a four-year period among children in areas receiving the vaccine.
Building a broader toolbox for malaria
Based on these results, the currently available vaccines will likely not be effective enough at reducing malaria parasite infections among African adults to be part of a malaria elimination strategy in endemic countries. Exploring a portfolio of products and strategies—including approaches that target the Plasmodium parasite throughout different stages of its lifecycle—will be critical to achieving malaria elimination and eradication.
“We’ve made major advances in the prevention, diagnosis, and treatment of malaria, but much is still unknown,” said Ashley Birkett, Global Head of Bacterial & Parasitic Diseases at PATH’s Center for Vaccine Innovation and Access. “Studies like this one are essential to inform the development of products that are effective and fit-for-purpose in malaria-endemic countries.”
“Studies like this one are essential to inform the development of products that are effective and fit-for-purpose in malaria-endemic countries.”— Ashley Birkett, Global Head of Bacterial & Parasitic Diseases at PATH
Sometimes, the most valuable insights come from the studies that don’t go as anticipated. We don’t know the answers until we ask the questions—and when results defy our expectations, they challenge our assumptions and open new paths forward.
“The current malaria vaccines are expected to save tens of thousands of young lives in high-burden countries,” continued Dr. Birkett. “And as their scale-up continues, further research on the existing vaccines, as well as next-generation vaccine approaches, will keep the world pushing towards eradicating malaria for good.”
