Researchers from the Leiden University Medical Center (LUMC) have created a new version of a malaria vaccine that consists of genetically weakened parasites. They have also received permission to test this vaccine in humans. The protection of an earlier version of this malaria vaccine was disappointing. Is the new vaccine more successful? The researchers think so and write why in NPJ Vaccines.
It was world news when the WHO approved GlaxoSmithKline’s first malaria vaccine last year. And that is not surprising, it is estimated that more than 240 million people worldwide are infected with the malaria parasite and on average more than 600,000 people die from the disease each year, many of which are children under the age of 5. This first vaccine shows a protection of 30 to 50%. “That was of course very good news,” says parasitologist Chris Janse. “But to really stop the spread, higher protection is needed. The target is 75%.”
Weakened parasites
Janse does not think it is surprising that there is not yet a vaccine with a high protection. “Most vaccines that have been tested contain only one or a few proteins from the parasite. This makes it difficult to kill all parasites. In addition, these proteins undergo changes all the time, so it is very difficult to make a vaccine that works for a long time,” he says. That is why Janse and colleagues use a different strategy. They are making a vaccine with genetically weakened malaria parasites, and have now renewed it.
Study in humans
The new version of the vaccine works very well in the lab. “We therefore quickly initiated the application for studies with humans,” says Janse. After permission, they immediately started the clinical study, in collaboration with LUMC professor Meta Roestenberg and Radboudumc, in which healthy participants are vaccinated with the genetically weakened parasites and then infected with malaria. A unique study design with which the LUMC had a world first with the previous vaccine. The results of this study are currently being compared with those of the earlier vaccine. “It is very exciting whether this vaccine actually works much better,” says parasitologist Blandine Franke-Fayard. Those results are expected next year.
DNA scissors
But how exactly does such a vaccine work? “A normal malaria parasite enters the human blood through a mosquito bite and travels to the liver. Here the parasite multiplies and then leaves the liver again in large numbers. That is also the moment when you get sick,” explains Janse. “If we can prevent the parasite from leaving the liver and getting back into the blood, the body can build an immune response against the parasite without making you sick.”
For more than 15 years, the researchers scoured the parasite’s DNA in search of genes responsible for leaving the liver. “In the end we found a handful of suitable genes, which we then cut from the DNA with molecular scissors. We saw that these genetically modified parasites managed to find their way to the liver, but indeed did not leave the liver and then died,” says Franke-Fayard.
Live longer in the liver
Their first vaccine did exactly this, but it turned out not to provide the desired protection in people after a malaria infection. Why would the new vaccine do that? Janse: “In the previous vaccine, we had cut genes from the DNA so that the weakened parasites remained in the liver for a maximum of 2 days before they died. Probably too short to build up a good immune response.” Now we have managed to delete another gene that allows the parasites to grow and multiply in the liver for 7 days, but then do not leave the liver. Experiments have already shown that these renewed weakened parasites are more visible to the immune system and lead to a better immune response. So hopeful results. “But we’ll have to wait and see whether this is also the case with humans,” Janse concludes.
Read the full article in NPJ Vaccines.