A new malaria vaccine has shown promising preliminary results in a large trial in four African countries, raising hopes that an additional tool may soon be available to help control the deadly disease. The vaccine, called R21/Matrix-M and developed by Oxford University researchers, produced similarly impressive results in a small trial last yearbut the current study put a more stringent test to its defense.
Initial data from the trial, reported yesterday at the American Society of Tropical Medicine and Hygiene meeting in Seattle, suggest the vaccine has an efficacy higher than 70% in regions where malaria is a year-round threat, as well as in places where the disease is more seasonal. “The results were very exciting,” said DeAnna Friedman-Klabanoff, a malaria vaccine researcher at the University of Maryland School of Medicine who was not involved in the study.
But she and other scientists caution that it’s not yet clear how long the vaccine’s protection might last.
The plasmodium The parasites that cause malaria have a complex life cycle with different, changing stages in the liver, in the blood and in the mosquitoes that carry the disease. This 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), called RTS,S or Mosquirix, offers only partial protection, especially in areas where malaria is a year-round threat. Its effectiveness drops to around 35% after 4 years – so low that the WHO first organized a multi-year pilot rollout in three African countries before deciding to recommend the vaccine’s wider use on the continent last year.
Both Mosquirix and R21/Matrix-M contain protein from plasmodiumthe surface of the blood stage bound to a protein from the hepatitis B virus, but the R21 vaccine includes a different immunostimulating agent, known as an adjuvant, than Mosquirix.
The earlier R21/Matrix-M study showed that three doses given every 4 weeks offered more than 70% efficacy after 1 year in 450 children in Burkina Faso. But the vaccine is given at the start of the rainy season, which lasts less than half the year and when almost all malaria cases occur. In September, the team reported additional data showing that children in this study who received a booster, again at the start of the rainy season, were protected for a second year. But researchers have not yet reported data on whether the vaccine’s protection lasts without a booster.
Watchers eagerly awaited the results of the larger study, which included 4,800 children in five locations in Burkina Faso, Mali, Kenya and Tanzania with different patterns of exposure to malaria. According to interim data presented yesterday, last year’s results are being maintained – 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 efficiency is 75%.
But it’s not yet clear whether the defense has staying power. Robert Sauerwein, a malaria vaccine researcher at Radboud University, notes that in regions with seasonal malaria, the main protective effect appears to be in the first 100 days after vaccination. New cases in the placebo arm of the trial then equalize, “so the duration of protection is difficult to estimate.” In areas with more constant exposure to parasite-carrying mosquitoes, “there is clear protection,” Sauerwein says, but transmission rates are generally low, so it’s hard to say how robust the results are, he says.
Faith Osier, a vaccine expert at Imperial College London, noted that some children in the phase 3 trial did not receive their third dose as late as April, and the results presented were collected by September 1. That means “the tail has only been vaccinated for 6 months,” she says. “It’s too early to see the results.”
Hill told the meeting that his group continues to collect data and plans to publish more complete results before the end of the year. The team hopes to have the vaccine approved for widespread use in the first half of 2023, he said. The world’s largest vaccine maker, the Serum Institute of India, has already agreed to manufacture the injections once they are approved and could produce more than 180 million doses a year, about 30 times the amount of Mosquirix produced annually, Hill noted on 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’ll need booster doses and how often,” Friedman-Klabanoff says. “It can be a logistical challenge.” Still, she adds, “Overall, the results are really exciting and encouraging. We are getting closer to a highly effective malaria vaccine.
With reporting by Jocelyn Kaiser.