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A malaria vaccine based on genetically modified parasites is worth developing further, according to the first study to test the new approach in humans.
Six volunteers were exposed to the malaria parasite Plasmodium falciparum, rendered harmless by genetic modification, through the bite of Anopheles mosquitoes. All six developed antibodies against the parasite without getting infected, reports the proof of concept study, published in Vaccine this month (11 September).
“While the existing treatment of parasites uses radiation, our approach focuses on fully defined gene deletions that can be tweaked to induce optimal immunity.”
Stefan Kappe, Seattle Biomedical Research Institute
But at higher doses one volunteer was infected — indicating that the technique for weakening the parasites needs perfecting before further trials can be carried out.
"Our approach is to genetically engineer parasites by deletion ofspecific genes that are critical for their replication in the liver," Stefan Kappe, a professor at the Seattle Biomedical Research Institute, United States, and one of the authors of the study, tells SciDev.Net.
"The genetically attenuated parasites can infect the liver, but cannot complete their development and therefore cannot infect the red blood cells. We call this the 'can check in but cannot check out' approach."
Other researchers have tried a similar approach by irradiating the parasites.
"But there is a critical difference," explains Kappe. "While the existing treatment of parasites uses radiation to cause random mutations in the parasite genome, our approach focuses on fully defined gene deletions that can be tweaked to induce optimal immunity. This way we don't rely on chance … but, rather, we design it."
But he says that it is too early to talk about mass implementation of the vaccine. One challenge is figuring out how to produce the weakened parasites in large enough numbers.
"Currently, they can only be made in mosquitoes, but we are working on making them in tissue culture," says Kappe.
Brian Greenwood, professor of clinical tropical medicine at the UK-based London School of Hygiene & Tropical Medicine, believes that the new experimental vaccine "is a valid approach to the development of a human malaria vaccine but it still has a long way to go".
For example, he says, while the study demonstrated that an immune response is triggered by these weakened parasites, it did not then expose volunteers to infectious malaria parasites to show that they would indeed be protected.
There are also safety concerns. "It would be a disaster if a large number of people were immunised with a parasite that had not been weakened sufficiently to prevent it causing clinical malaria in some recipients," says Greenwood.
Kappe says: "Genetic engineering of the parasite is still an art and very cumbersome, but we are getting better at it".
> Link to study abstract in Vaccine