The revamped malaria vaccine can be tested on humans

A normal malaria parasite enters human blood through a mosquito bite and travels to the liver

Researchers from Leiden University Medical Center (LUMC) have created a new version of a malaria vaccine that consists of genetically weakened parasites. They also received permission to test this vaccine on humans. The protection of an older version of this malaria vaccine was disappointing. Is the new vaccine more successful? Researchers think so and write why in NPJ Vaccines.

It was world news when the WHO announced it last year GlaxoSmithKline’s first malaria vaccine approved. And unsurprisingly, it is estimated that over 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 whom are children under the age of 5. This first vaccine shows 30 to 50% protection. “Obviously it was great news,” says parasitologist Chris Janse. “But to really stop the spread, more protection is needed. The goal is 75% “.

Weakened parasites
Janse doesn’t find it surprising that there isn’t a high-protection vaccine yet. “Most of the vaccines that have been tested contain only one or a few proteins of the parasite. This makes it difficult to kill all parasites. Also, these proteins undergo constant changes, so it is very difficult to make a vaccine that works for a long time, “he says. That’s why Janse and colleagues use a different strategy. They are making a vaccine against genetically weakened malaria parasites and now they have renewed it. .

Study in humans
The new version of the vaccine works very well in the laboratory. “We therefore quickly initiated the application for studies with humans,” says Janse. After authorization, 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 that allows LUMC to use the previous vaccine world premiere I had. The results of this study are currently being compared with those of the previous vaccine. “It’s very exciting if this vaccine really works much better,” says parasitologist Blandine Franke-Fayard. These results are expected next year.

DNA scissors
But how exactly does such a vaccine work? “A normal malaria parasite enters human blood through a mosquito bite and travels to the liver. Here the parasite multiplies and then exits again in large numbers from the liver. This is also the time when you get sick, ”explains Janse. “If we can prevent the parasite from leaving the liver and returning to the blood, the body can build an immune response against the parasite without making you sick.”

For more than 15 years, researchers have searched the parasite’s DNA for genes responsible for exiting the liver. “We eventually found a handful of suitable genes, which we then cut out of the DNA with molecular scissors. We saw that these genetically modified parasites made it to the liver, but they did not actually leave the liver and then died, “says Franke-Fayard.

Live longer in the liver
Their first vaccine did exactly that, just as it turned out not the desired protection in humans after a malaria infection. Why should the new vaccine do this? Janse: “In the previous vaccine, we cut the genes from the DNA so that the weakened parasites stayed in the liver for up to 2 days before they died. Probably too short to build a good immune response. “We have now managed to eliminate another gene that allows parasites to grow and multiply in the liver for 7 days, but then do not leave the liver. Experiments have already shown that these parasites renewed and weakened are more visible to the immune system and lead to a better immune response. So hopeful results. “But we will have to wait and see if this also applies to humans,” concludes Janse.

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