Malaria vaccine using live modified parasites shows promise in trial

An experimental malaria vaccine that consists of living parasites weakened by the deletion of three key genes has produced promising results in a small trial involving 16 volunteers. The researchers behind the study think that live vaccines of this kind will produce better protection than those based on single proteins, such as the RTS,S vaccine, which last year became the first ever malaria vaccine to be approved.

“Live whole organisms have always been better,” says Stefan Kappe at the Seattle Children’s Research Institute. “They stimulate the immune system in so many different ways.”

After a person is bitten by a malaria-infected mosquito, the malaria parasites (Plasmodium falciparum) travel to the liver and begin to multiply there. This liver stage causes no symptoms. It is only when the parasites start infecting red blood cells that symptoms appear.

Kappe and his team deleted three genes in the parasite that are essential for it to leave the liver and infect blood cells. These genetically modified parasites can’t cause severe disease, nor can they be transmitted to other people. “The parasite can’t come out of the liver and cause blood-stage infections,” says Kappe.

The team “vaccinated” 16 volunteers by allowing them to be bitten at least 200 times on three or five occasions by mosquitoes infected with the modified parasite.

When they were later exposed to mosquitoes infected with unmodified parasites, half of these volunteers didn’t develop blood-stage infections. By contrast, four out of five unvaccinated volunteers exposed to wild-type parasites developed blood-stage infections.

Kappe says these lab results can’t be directly compared with the results of field trials of the RTS,S vaccine, which suggest it is around 30 per cent effective. For one thing, the live vaccine had to be delivered by mosquito bites. The team is working on ways of breeding parasites outside mosquitoes and injecting them directly.

What’s more, the team has used CRISPR to modify parasites so they can replicate for longer in the liver but still can’t leave it. This improved experimental vaccine has produced stronger immune responses in animal tests that have not yet been published, says Kappe.

“Our hope is that this vaccine will give very potent protection, 100 per cent hopefully for at least six to 12 months,” he says.

Another malaria vaccine under development, called R21, was last year reported to be 77 per cent effective in trials. It targets the same, single malarial protein as RTS,S.

The problem with targeting a single protein is that mutations in these proteins can reduce the effectiveness of the vaccines, says Kappe. That is exactly what has happened with vaccines targeting the spike protein of the SARS-CoV-2 coronavirus.

There have been many previous efforts to develop living malarial vaccines. One approach is to zap the parasites with radiation to make them incapable of multiplying. Another is to infect people with wild-type parasites and then give them antimalarial drugs. Using genetically modified parasites will be safer, the researchers say.

Some vaccines that consist of live attenuated viruses can revert back to being dangerous. That is why there have been polio infections in the US and the UK recently. However, in these cases the vaccine virus differs from the wild virus by just a few mutations. By contrast, the live parasites used in the vaccine have had entire genes removed, so there is no chance of reversion, says Kappe.