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Malaria vaccine using modified live parasites shows promise in trial

A ‘live vaccine’ containing malaria parasites with key genes deleted has produced promising results in a small early trial

Health


24 August 2022

Female Anopheles albimanus mosquitoes carry malaria.

IanDagnall Computing / Alamy

An experimental malaria vaccine consisting of live 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 believe that live vaccines of this type will produce better protection than those based on individual proteins, such as the RTS,S vaccine, which last year became the first malaria vaccine to be approved.

“Whole living organisms have always been better,” he says. Stephen Cap at the Seattle Children’s Research Institute. “They stimulate the immune system in 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 stage of the liver does not cause symptoms. Only when the parasites begin to infect the red blood cells do symptoms appear.

Kappe and his team removed three genes from the parasite that are essential for it to leave infected liver and blood cells. These genetically modified parasites cannot cause serious illness or spread to other people. “The parasite can’t get out of the liver and cause blood-stage infections,” says Kappe.

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

When later exposed to mosquitoes infected with unmodified parasites, these volunteers did not develop blood-stage infections. In contrast, four out of five unvaccinated volunteers exposed to wild-type parasites developed blood-stage infections.

Kappe says these lab results cannot be directly compared to results from field trials of the RTS,S vaccine, which suggest it is about 30 percent effective. For one thing, the live vaccine had to be administered by mosquito bites. The team is working on ways to breed parasites off mosquitoes and inject them directly.

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

“Our hope is that this vaccine will provide very strong protection, hopefully 100 percent for at least six to 12 months,” he says.

Last year it was reported that another malaria vaccine in development, called R21, was 77 percent effective in trials. It targets the same unique malarial protein as RTS,S.

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

There have been many previous efforts to develop live malaria vaccines. One approach is to kill the parasites with radiation so they can’t multiply. Another is to infect people with wild-type parasites and then give them antimalarial drugs. The use of genetically modified parasites will be safer, the researchers say.

Some vaccines that consist of live attenuated viruses can again be dangerous. This is why there have recently been polio infections in the US and UK. However, in these cases, the vaccine virus differs from the wild virus by a few mutations. By contrast, the live parasites used in the vaccine have had entire genes deleted, so there’s no chance of reversal, Kappe says.

Magazine Reference: Science Translational Medicine, DOI: 10.1126/scitranslmed.abn9709

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