Knocked Out Gene May Lead To Malaria Vaccine

By Megan Dann Fesinmeyer

For millennia, humans have lived in the shadow of malaria. Insecticide-treated bed nets and drugs are only marginally effective at preventing and treating the disease, and the Centers for Disease Control and Prevention estimates that malaria kills between 700,000 to 2.7 million people worldwide each year.

At one Northwest laboratory, a novel approach has produced a new contender in the race to find a malaria vaccine. In January, researchers in Seattle, Wash. and Germany published their discovery that genetically modified malaria parasites may be an effective vaccine.

"It's a big step forward in creating an attenuated whole-organism vaccine,” says Stefan Kappe, a scientist at the Seattle Biomedical Research Institute. Kappe and colleagues at the University of Heidelberg published their findings in the journal Nature.

The researchers injected mice with genetically altered parasites, then exposed these mice to mosquitos carrying infectious malaria parasites. None of the mice got sick.

The idea of a live-attenuated malaria vaccine is nothing new. Kappe notes that attacking the entire malaria sporozoite genome with radiation is another way to produce an effective, if unpredictable, live organism vaccine. Kappe and his colleagues achieved a similar result with the malaria genome, knocking out a single gene.

"What is new in our research is that we can now precisely manipulate one or two genes, and have the same effect. And that makes it much more controllable, much more safe, and much more predictable in terms of the parasite's behavior,” says Kappe.

The deleted gene is UIS3, one of several identified by the team's previous search for genes that are active only in parasites infecting liver tissue. Although this research suggests that knocking out UIS3 is enough to stop the parasite in its tracks, Kappe will leave nothing to chance.

"To create a truly safe parasite, we want to delete more than one gene that is necessary for liver stage development,” says Kappe. He hopes this one-two punch will render the parasite harmless, while still inducing immunity to future infection.

The team now aims to repeat the experiment with human volunteers and P. falciparum, the most lethal malaria species that infects humans. Even if human trials are successful, "There are still formidable challenges, both technical and safety-related, to be solved before any live vaccine can be used in the field,” says Robert Ménard, director of the Malaria Biology and Genetics Unit at the Institut Pasteur in Paris.

Despite these remaining hurdles, a malaria vaccine may be the only economically feasible solution in sub-Saharan Africa, where more than 90 percent of the lethal malaria cases occur. "They can't afford the drugs, they can't afford the bed nets,” notes Kappe. "That's why a vaccine is the best solution, because it will be the cheapest way of protecting people against malaria.”

Megan Dann Fesinmeyer is a graduate student at the Institute for Public Health Genetics at the University of Washington.

Image:

Top: Stefan Kappe of the Seattle Biomedical Research Institute found that a live attenuated malaria vaccine is effective in mice.