A first-ever malaria vaccine tested in children in sub-Saharan Africa cut the risk of infection with malaria by about half, researchers announced in a teleconference on Tuesday.
Scientists working in a public-private partnership involving GlaxoSmithKline (GSK) Biologicals, the PATH Malaria Vaccine Initiative and the Bill and Melinda Gates Foundation, at 11 sites in Africa, reported that the experimental vaccine known as RTS,S was 56% effective in protecting children aged 5 to 17 months from infection with malaria a year after immunization. The vaccine was also 47% effective in preventing severe cases of the disease. The results of the late-stage trial were published online by the New England Journal of Medicine.
“This vaccine shows an important impact in terms of protection against clinical and severe malaria,” Christian Loucq, director of the PATH Malaria Vaccine Initiative, tells TIME, noting that among the first 6,000 children who received the vaccine (or a control vaccine), researchers saw 1,500 cases of clinical malaria among those in the control group, compared with only 750 cases — or half — among those receiving the malaria vaccine.
The trial is not complete. The researchers are continuing to gather data on a younger group of infants, aged 6 to 12 weeks, who are being vaccinated as well. This group would be the target population for the malaria vaccine, should it prove effective, since they take part in routine public health inoculation programs. Both age groups will be followed for nearly three years to track malaria infections and to see how long protection lasts; researchers are also collecting additional safety data in infants. The trial, which involves a total of 15,460 children, will be completed in 2014.
The next question the scientists hope to answer is whether an efficacy of around 50%, as the current trial shows, is good enough to start vaccinating youngsters in countries where malaria is endemic. In sub-Saharan Africa, the mosquito-borne disease infects millions each year and kills 800,000 youngsters annually. But other vaccines that children receive against childhood infections, such as measles and rotavirus, reach efficacy rates of 70% to more than 90%.
At its current power, the candidate vaccine “potentially translates to tens of millions of malaria cases among children that can be averted annually,” Dr. Tsiri Agbenyega, head of the malaria research unit at the Komfo-Anokye Hospital in Ghana and chair of the RTS,S Clinical Trials Partnership Committee, told reporters during Tuesday’s briefing. “The study found that RTS,S also reduced risk of severe malaria by 47%. That’s remarkable when you consider that there has never been a successful vaccine against a human parasite, nor against malaria.”
Still, says Dr. Regina Rabinovich, director for infectious diseases of the global health program at the Bill & Melinda Gates Foundation, “Would I prefer to see a 100% effective vaccine? Absolutely.”
Whether or not a malaria vaccine can achieve that level of effectiveness isn’t clear. The development team is confident that the percentage may improve as the RTS,S trials continue, particularly in younger children. In addition, the trial is also testing whether children vaccinated with all three doses of the vaccine, plus a booster 18 months later, are better protected than children receiving just the malaria doses alone.
Even getting this far took decades of research and a $300 million investment on GSK’s part, not to mention financial commitments from sponsors of the multicenter trial, which spans seven African countries. The vaccine is the first against a parasite, an organism that tends to be more complex than the bacteria and viruses that can cause infectious diseases. The malaria parasite, Plasmodium falciparum, also adopts a complicated life cycle once inside a human host in order to protect itself from destruction by the immune system. Once introduced into the bloodstream through bites from mosquitoes that carry the bug, P. falciparum immediately targets the liver, where it reproduces and sends a more streamlined form to infect red blood cells.
The RTS,S vaccine is designed to intercept P. falciparum‘s journey to the liver by binding it to antibodies that prevent it from reaching the organ; once the parasite infects the liver, it’s difficult to extract. “In the liver, they can escape the immune system, so there is only a short period of time during which the antibodies can act,” says Loucq. “So we need a high level of antibodies to be sure they will act during the short period of time before the parasite reaches the liver.”
Work on the vaccine can be traced back to the 1960s, when researchers at New York University first identified the portion of P. falciparum that would make a good target for vaccine-delivered antibodies. It’s taken decades of research, however, to act on that information and find the right section of the parasite’s coat that the bug doesn’t easily change to bypass a vaccine.
And it will take several more years to gather enough data to support the safety and efficacy of the vaccine, as well as work out how the inoculation will be distributed in public health programs in developing countries. GSK’s CEO Andrew Witty has committed to investing another $50 to $100 million to see the research project through and to supplying the vaccine at the lowest possible price to those most in need. A 5% profit the company plans to build into the price of the drug will be re-invested in neglected-disease research, and Witty said the company would forgo its profits on the vaccine.
But even if the vaccine proves effective and can be distributed at a reasonable price, public health experts stressed that it shouldn’t be the final and only answer to fighting malaria. The study participants were also using existing malaria interventions, such as insecticide-treated bed nets, and taking part in indoor spraying for mosquitoes. These preventive measures should remain an important part of keeping rates of the disease down. “It’s very important that when the vaccine is deployed, that it’s deployed with proven interventions of malaria control,” Dr. Mary Hamel of the Centers for Disease Control and Prevention’s malaria branch said during the briefing. “This trial was conducted in the setting of good control measures, and showed added benefit with those measures in place. And it’s how we should expect such a vaccine would be deployed at this time.”
Whether the new malaria vaccine will indeed make its way onto the childhood immunization schedule for children in developing nations won’t be clear for another few years. But the current results are a promising step in the right direction.