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Sweet Success Against Malaria

A new vaccine targeting malaria toxin could prevent one of the world’s deadliest diseases.
January 27, 2003

A potential malaria vaccine that targets a toxin responsible for symptoms of the disease has been created by researchers at the Massachusetts Institute of Technology and Australia’s Walter and Eliza Hall Institute of Medical Research. The results of a study on the new vaccine were reported in the journal Nature on August 15.

A successful malaria vaccine could help stem the 300 million acute illnesses and two million deaths the disease causes each year. “Malaria is probably the world’s most serious infectious disease, rivaled by AIDS and tuberculosis,” says Hall Institute microbiologist Louis Schofield, a collaborator on the project. Schofield hopes the new vaccine will prove a highly effective way to control the most severe-and often fatal-symptoms of malaria. But even if it works, he estimates that ten years could pass before the vaccine is fully tested and approved, though the process may be accelerated.

The disease is caused by a single-celled parasite transmitted via mosquito bites. Typical symptoms include fever, headache and vomiting. Untreated, the parasites can kill by causing accumulation of fluid in the lungs, acidosis, or cerebral malaria, in which infected red blood cells block blood flow to the brain. Malaria is endemic to many parts of the world, and it is difficult and expensive to continuously treat the disease. In addition, the parasites have developed resistance to many of the existing antimalarial drugs.

As a result, vaccines to prevent the disease are attractive option. While many malaria vaccines have performed well in experiments with mice, most have not succeeded as well in later human trials. “Developing malaria vaccines is highly desirable, but very problematic,” Schofield says. The reason is that most vaccines are designed to target and kill the organism causing the illness. But the malaria parasite hides inside human cells, evading the immune system. Schofield and his MIT collaborator, chemist Peter Seeberger, are optimistic that their vaccine may have greater success because its goal is not to eliminate the parasite, but simply to block the toxin causing many symptoms of the disease. This might even eventually allow the immune system to clear the infection on its own.

About ten years ago, Schofield isolated complex sugar molecules thought to be the toxin responsible for many of malaria’s worst symptoms. In 1999, he began collaborating with MIT chemist Peter Seeberger to create and test a vaccine based on the suspected toxin. Complex sugars have been notoriously difficult to synthesize in labs. Seeberger had developed new technology that significantly sped up the process and used it to make a synthetic version of the toxin. Schofield then immunized mice with the synthetic sugar; 75 percent of immunized mice survived infection with the malaria parasite, while untreated mice died.

The anti-toxin approach has attracted attention in the malaria research community. “If the first goal is to prevent severe disease and death in young children in the developing world, then the idea of blocking the mechanism whereby this serious disease develops is a very appealing one,” says Steve Hoffman, former head of the U.S. Navy malaria vaccine program. “[Schofield] has made a remarkable achievement taking it this far, and it needs to be further evaluated.”

Two primate trials of the anti-toxin vaccine are planned within the next year, in Holland and at the Centers for Disease Control and Prevention in Atlanta. Seeberger says that the Gates Foundation as well as the World Health Organization and the National Institutes of Health have expressed interest in supporting tests of the vaccine.

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