Knocking Out Malaria?
Genetically engineered vaccine shows promise

Context: The world’s first vaccines were made from weak forms of disease-causing microbes. A more modern approach is to instead use one or a few of a microbe’s signature molecules. But the malaria para­site – Plasmodium – foils this strategy because at different developmental stages it has different surface proteins. However, the older approach also poses problems: insufficiently weakened parasites might bring on the disease, but overly weakened ones are ineffective. Researchers led by Kai Matuschewski at the Heidelberg University School of Medicine in Germany and Stefan Kappe at the Seattle Biomedical Research Institute have announced a promising mixture of new and old. They have, for the first time, made a malaria vaccine by weakening the parasite through genetic engineering.

Methods and Results: Plasmodium constantly changes both appearance and address, moving from mosquitoes’ guts to their salivary glands to mammals’ liver cells to their blood. With the newly sequenced Plasmodium genome as a guide, the researchers looked for genes the parasite needs to move from liver to blood. They found such a gene and completely deleted it from the version of Plasmodium that infects rodents. Then, they injected rats and mice with the genetically modified parasites. None got malaria. Two months after vaccination, the rodents were injected with 50,000 nonmodified parasites (the equivalent of hundreds of bites from infected mosquitoes). Encouragingly, none got sick.

Why it Matters: Malaria kills millions annually; the sickness stifles development in afflicted countries by keeping people from work and school and by draining health resources. The vaccine developed by Matuschewski and colleagues must still show that it is able to prevent disease in humans and for the long term. In mice, the vaccine must be administered two or three times, delivering thousands of parasites that can be grown only in mosquitoes’ salivary glands. To save lives, future whole-parasite vaccines must be more potent and easier to produce. Or perhaps knowledge gleaned from genetically modified vaccines will inspire more successful versions of other vaccines. If either happens, this devastating disease could be eradicated within a generation.

Source: Mueller, A. K., et al. 2005. Genetically modified Plasmodium parasites as a protective experimental malaria vaccine. Nature 433:164–7.