A new vaccine against malaria showed promising preliminary results in a large trial in four African countries, boosting hopes that an additional tool may soon be available to help control the deadly disease. The vaccine, named R21/Matrix-M and developed by researchers at the University of Oxford, produced similarly impressive results in a small trial last year, but the current study posed a stiffer test of its protection.
Initial data from the trial, reported yesterday at the American Society of Tropical Medicine and Hygiene meeting in Seattle, suggest the vaccine had an efficacy higher than 70% in regions where malaria is a threat year-round as well as in places where the disease is more seasonal. “The results were very exciting,” says DeAnna Friedman-Klabanoff, a malaria vaccine researcher at the University of Maryland School of Medicine who was not involved in the study.
She and other scientists caution, however, that it is not yet clear how long the vaccine’s protection might last.
The Plasmodium parasites that cause malaria have a complex life cycle with different, shape-shifting stages in the liver, in blood, and in the mosquitoes that transmit the disease. That makes them much more difficult to target with a vaccine than diseases caused by bacteria or viruses. The only malaria vaccine authorized by the World Health Organization (WHO), named RTS,S or Mosquirix, only offers partial protection, especially in areas where malaria is a threat year-round. Its efficacy drops to about 35% after 4 years—so low that WHO first staged a multiyear pilot rollout in three African countries before deciding to recommend the shots’ wider use on the continent last year.
Both Mosquirix and R21/Matrix-M contain a protein from Plasmodium’s blood-stage surface coupled with a protein from the hepatitis B virus, but the R21 vaccine includes a different immune-boosting agent, known as an adjuvant, from Mosquirix.
The earlier R21/Matrix-M trial demonstrated that three doses given 4 weeks apart offered more than 70% efficacy after 1 year in 450 children in Burkina Faso. But the vaccine was given at the start of the rainy season, which lasts less than half the year and is when almost all malaria cases occur. In September, the team reported additional data showing children in that study who received a booster, again at the start of the rainy season, were protected for a second year. But the researchers have not yet reported data on whether the vaccine’s defense holds up without a booster.
Observers had been eagerly awaiting results from the larger trial, which involves 4800 children at five sites in Burkina Faso, Mali, Kenya, and Tanzania with different patterns of malaria exposure. According to the interim data presented yesterday, last year’s results hold up—at least for now. In areas with year-round malaria transmission, the vaccine showed 73% efficacy after an average of 270 days, Adrian Hill, a vaccine expert at Oxford’s Jenner Institute who is leading the project, told the meeting. In areas of seasonal transmission, the efficacy was 75%.
But whether the protection has staying power is still not clear. Robert Sauerwein, a malaria vaccine researcher at Radboud University, notes that in the seasonal malaria regions, the main protective effect seems to be in the first 100 days postvaccination. After that, new cases in the trial’s placebo group leveled off, “so duration of protection is hard to assess.” In areas with more constant exposure to parasite-carrying mosquitoes, “there is clearly protection,” Sauerwein says, but transmission levels were generally low, so it is hard to tell how robust the results are, he says.
Faith Osier, a vaccine expert at Imperial College London, notes that some children in the phase 3 trial received their third dose as late as April, and results presented were collected through 1 September. That means “the tail end has only been vaccinated for 6 months,” she says. “It’s very early days in terms of looking at the results.”
Hill told the meeting that his group is continuing to collect data and plans to publish more complete results before the end of the year. The team hopes the vaccine could be approved for wide use in the first half of 2023, he said. The world’s biggest vaccinemaker, the Serum Institute of India, has already agreed to produce the shots once they’re approved and can churn out more than 180 million doses per year, about 30 times the amount of Mosquirix manufactured annually, Hill noted at the meeting. He estimated the vaccine would cost between $3 and $4 per dose.
But if R21’s protection turns out not to be very durable, the question becomes “whether we’re going to need booster doses and how often,” Friedman-Klabanoff says. “That can be logistically challenging.” Still, she adds, “Overall the results are really exciting and encouraging. We’re getting closer to a highly effective vaccine against malaria.”
About the author
