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The first study showing that a live malaria parasite could one day be used as a vaccine to protect people from the disease was published yesterday (5 December).

By modifying the genes of a form of the parasite that causes malaria in rodents, the researchers were able to prevent it from moving from the rats' liver to their blood stream. Once in the blood stream, the parasite normally enters red blood cells, causing symptoms of disease. It is also from there that it can be transmitted to others, through a new mosquito bite.

The researchers were able to trap the parasite in the liver by 'knocking out' one of the parasite's genes that earlier research had suggested was important at the infective stage of the parasite's life cycle.

The paper's lead author, Ann-Kristin Mueller of the Heidelberg University School of Medicine, in Germany, told SciDev.Net the study proves that, in principle, the deletion of a single gene could be enough to create a form of the parasite that is unable to affect human health.

Such a weakened parasite could be used as a vaccine by giving the immune system a window of opportunity to develop the ability to recognise and repel future infections of normal malaria parasites before they can pose threats to health.

To confirm the potential for this, Mueller and her colleagues infected laboratory rats with normal malaria parasites after first injecting them with the genetically modified version. They found that the rats stayed healthy even when infected with 50,000 parasites two months after receiving the third of three doses of modified parasites.

Mueller says the next step would be to target the same gene in one of the human forms of malaria, and see how the human immune system deals with the modified parasite. Also, she says it is important scientists understand better the role of the deleted gene.

The researchers are also looking at about 30 other rodent malaria genes that also seem to be particularly important during infection. They say the recent availability of complete genetic maps of the malaria parasite should help develop a live vaccine based on more precise genetic modifications.

"This is exciting work," says Sanjeev Krishna, a professor of parasitology at St. George's Hospital Medical School in London. "It proves the concept that a live parasite can be used as a vaccine against malaria."

He adds, however that a human vaccine using the gene deletion approach is still some way off. "Translating this into something given to children — that takes time."

Krishna also warned that relying on a single deleted gene creates the risk that some of the modified parasites could overcome the need for it and 'escape' from the liver to cause malaria.

"It only takes one parasite to cause the disease," Krishna told SciDev.Net.

Mueller's colleagues are based at the Heidelberg University School of Medicine, Germany, the Seattle Biomedical Research Institute, United States, and the University of Washington, also in Seattle. Their research was partially funded by the Bill and Melinda Gates Foundation and the US National Institutes of Health.

Link to abstract of paper by Ann-Kristin Mueller et al

Reference: Nature Advance Online Publication doi:10.1038/nature03188

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