A new and highly effective vaccine for malaria has shown success in its first human trial. The phase 1 study saw a strong immune response in 10 healthy volunteers.
The vaccine – called GAP3KO - was created by genetically engineering the malaria parasite to make it weaker. Scientist removed the three genes needed for it to successfully infect and cause disease in humans. None of the participants developed malaria symptoms and all demonstrated a strong protective antibody response.
Malaria remains one of the world's biggest killers despite huge efforts to protect people at risk. In 2015, there were 212 million cases and 429,000 deaths. Since 2010, there has been a 29% reduction in mortality rates thanks to prevention and control measures – but it is largely accepted that without and effective vaccine, the disease cannot be eradicated.
At present, there are a number of vaccines being developed, but at present even the most advanced only provide partial protection against the disease. Many current vaccines contain fragments of the malaria parasite, which is why they are only partially protective. A recent phase 3 trial of RTS,S/AS01, for example, was below the 75% protection threshold set out by the World Health Organization's Malaria Vaccine Technology Roadmap.
Previous studies on animals have shown that complete immunity to malaria can be achieved by immunisation with live parasites, but this poses a big problem when it comes to testing on humans – the potential to cause malaria.
In a study published in the journal Science Translational Medicine, researchers have announced the results of a small phase 1 study that tested a new vaccine on a small sample of healthy individuals. Unlike other vaccines, the team created a weakened version of the malaria parasite.
To do this, they removed the three genes required for the parasite to infect humans and cause disease. This 'tamed' version of the parasite is incapable of multiplying in the liver – but it is alive and able to stimulate an immune response. This means a person can build up a defence against, meaning when faced with the real malaria parasite, is protected from it – a strategy called attenuation.
Researchers created the genetically modified mosquitoes and, through their bites, the vaccine was administered to participants. None of the participants showed signs of infection in their blood. When their antibodies were transferred to mice who were subsequently infected, the malaria infection was blocked.
Study leader Sebastian Mikolajczak, from the Centre for Infectious Disease Research, said: "We had already good indicators in preclinical studies that this new 'triple knock-out' GAP (GAP3KO), which has three genes removed, is completely attenuated. The clinical study now shows that the GAP3KO vaccine is completely attenuated in humans and also shows that even after only a single administration, it elicits a robust immune response against the malaria parasite. Together these findings are critical milestones for malaria vaccine development."
Robert Seder, from the National Institutes of Health who was not involved in the research, said: "This report is a major advance in malaria vaccine development by providing the first evidence that genetically attenuated Plasmodium falciparum parasites are safe and immunogenic in humans. Future studies demonstrating protective efficacy will be the next critical milestone for continued development of this promising vaccine approach."
The next step will be to carry out a phase 1b trial of the vaccine using controlled human malaria infection. The researchers also note that because it can only be produced in mosquitoes, widespread application of the vaccine would be problematic because of the limited scalability.