Over the last year, as doctors battled to save Ebola patients, hundreds of thousands of other Africans were dying from a longer-lasting crisis. Malaria–eradicated in the U.S. around 60 years ago–is still the biggest killer of children in Africa. But a vaccine is finally getting closer.
The fight against malaria has been making progress in other ways, as more families start to use tools like bed nets to keep away the mosquitoes that spread the disease. But the new vaccine, called Mosquirix (or RTS,S) could add much-needed help. It works by triggering the immune system to defend against the malaria parasite twice–once when the parasite enters the bloodstream, and again when the parasite infects the liver.
“The range of interventions available today have indeed made progress in reducing malaria, but no one intervention has proven capable of serving as a ‘magic bullet,'” says Moncef Slaoui, head of the vaccine division at GlaxoSmithKline, the company that developed Mosquirix. “Each is imperfect, in different ways. We know that vaccines have historically offered one of the most effective means of preventing infectious diseases and saving lives. Yes, we need to strengthen existing interventions such as bed nets and anti-malarial medicines, but we also need to introduce new ones.”
The vaccine itself isn’t perfect yet–it works best in children over five months old rather than younger babies, and it only works some of the time. In trials with over 15,000 children, it had 32% efficacy, and that declined as kids got older. Still, because of the size of the problem, even partial efficacy could make a difference.
“When you consider the sheer scale of malaria, the reductions that we see with RTS,S are very meaningful,” says Slaoui. “Each year there are almost 200 million cases of malaria globally and almost 600,000 malaria deaths–nearly all in children under five in sub-Saharan Africa. If these numbers could be reduced by 40%, the benefit for Africa would be huge.”
The shots may also work better in real life than in the trials, where they were used in combination with bed nets and regular monitoring of infants and children. “In a real-life setting where malaria control may be less optimal, we expect the vaccine efficacy may be higher,” he says. In trials, the vaccine also worked better in places with higher malaria transmission.
There are challenges to overcome, like the fact that the vaccine requires booster shots to keep working–and it’s hard to get families to return on schedule. As it moves through the World Health Organization’s pre-qualification process, part of the research will involve figuring out the best way to implement the vaccine.
The vaccine has been a long time coming, with 15 years of development in the lab and another 15 for clinical trials. “No one has ever made a vaccine against a human parasite before, so we were creating the roadmap as we went along. The first challenge is that the [parasite] is a very evolved creature that has spent millennia learning how to best elude the human immune system,” says Slaoui.
Since the company began researching the problem in 1984 with its partners, its goal was to find a new approach than vaccines in the past, which had failed. “Our challenge was to find a secondary point of disabling the parasite: something more than the classical vaccine strategy to ‘kill it as it enters the blood stream upon a mosquito bite,'” he says.
Within a few minutes after a mosquito bite, the parasite can travel to the liver, where it hides for around five days before re-entering the bloodstream. At that point, it transforms and multiplies, ready to infect red blood cells and make someone sick–and possibly die. The new vaccine was designed to kill the parasite while it’s still in the liver, before it can do damage.
It works by giving the immune system more ways to fight off the parasite, through something called an “adjuvant” system that Slaoui compares to a country’s military. “The ‘regular’ form of defense is the simplest–artillery,” he says. “Most vaccines provide this level of protection. But, when we use the adjuvant, we give the immune system the equivalent of multiple defenses systems to use: Air Force, Marines, Navy, etc.”
The system took years to develop and validate, and then over a decade to test in clinical trials across seven countries, at sites that didn’t initially have the right infrastructure for testing. With the help of grants from the Gates Foundation, GlaxoSmithKline completed the trials.
On July 24, Mosquirix passed the last hurdle before the World Health Organization can consider approving it. The European Medicines Agency–the E.U. equivalent of the FDA–combed through the vaccine’s 250,000-page application and gave it the green light. The WHO will start to consider the drug this fall. Next year, if the WHO prequalifies it, GSK will apply to national health authorities to start providing the vaccine–a process that may take a couple of years.
The pharma company won’t profit from it (though they have been able to use some of the lessons learned for other commercial products, like their shingles vaccine). “We are determined that children should not be deprived of access to a malaria vaccine because their parents can’t afford it,” Slaoui says. GSK invested $350 million in developing the vaccine, and will sell it at the cost of manufacture, along with a small return of around 5% that will be invested in research for second-generation malaria vaccines or vaccines for other neglected diseases.