If the drug works in humans, it could become a more effective and longer lasting anti-malarial vaccine than those currently available, according to the researchers.
Details of the research will be presented next week (Aug. 21) in Boston at the 224th national meeting of the American Chemical Society, the world's largest scientific society. The study will be published in the Aug. 15 issue of Nature.
"This research represents an exciting new approach to controlling malaria by blocking the toxin that is responsible for so many deaths," says Peter H. Seeberger, Ph.D., associate professor of chemistry at the Massachusetts Institute of Technology in Cambridge, Mass. "We hope that this is the answer, but we don't know yet."
Tests of the new vaccine in monkeys are slated to begin soon, while tests on humans could begin within two years, said Seeberger, who is co-leader of the study along with his colleague, Louis Schofield, Ph.D., of the Walter & Eliza Hall Institute of Medical Research in Melbourne, Australia.
Although other vaccines have been developed and tested against malaria, none lasts for more than a few weeks. Most target proteins on the surface of the parasite, which has the ability to change its surface proteins and eventually resist the vaccine, according to Seeberger.
The new vaccine targets the toxin instead of the parasite. Although the parasite itself lives, it is rendered harmless by the destruction of its deadly toxin, he said.
One or two shots of the vaccine are expected to provide lasting protection against the disease. If necessary, its effectiveness could be enhanced by using it in combination with other vaccines that target the malarial parasite, Seeberger said.
Malaria is a life-threatening parasitic disease transmitted by the bite of the female Anopheles mosquito, which transfers deadly one-celled parasites to human blood in an effort to nurture her eggs. The disease can be caused by one of four different parasites. The most lethal is Plasmodium falciparum, which is also responsible for the majority of infections.
Louis Schofield recently discovered that, as part of its life cycle inside its human host, the parasite releases an inflammatory toxin that appears to trigger the fever, convulsions and deaths associated with the disease.
Previous studies by Seeberger's colleagues demonstrated that small amounts of the toxin — a tiny carbohydrate molecule called GPI — could be used to effectively immunize mice against infection and reduce fatalities. But the human immune system does not recognize such small molecules as foreign and cannot make antibodies to destroy them.
Seeberger and Schofield designed a synthetic version of the toxin and attached it to a protein molecule in hopes that the newly created complex would be large enough for the body to recognize so that an immune response could be launched against it.
When a group of healthy, unvaccinated mice were injected with blood containing a deadly malarial parasite, all died. But when the synthetic toxin was injected into a group of healthy mice and they were subsequently injected with the parasite, 65 to 95 percent survived.
The immunized mice also had enhanced protection from severe inflammatory conditions associated with the disease, including swelling of the brain, the researchers found.
Seeberger and his colleagues are continuing to refine their vaccine formulations to achieve a 100 percent survival rate. They hope that similar results will be seen in people.
According to the World Health Organization (WHO), malaria is one of the major public health problems, along with HIV/AIDS and tuberculosis, in the poorest regions of the world. More than 90 percent of deaths from malaria occur in Africa, mostly among infants and young children. It is estimated that the disease kills one African child every 30 seconds.
More recently, a dramatic surge in the number of malaria cases occurring among U.S. travelers to areas where the disease is common has been reported.
Funding for this research was provided by the National Institutes of Health, the United Nations Development Programme/World Bank/WHO Special Program for Research and Training in Tropical Diseases, the Human Frontiers of Science Program, the Howard Hughes Medical Institute, and the Australian National Health & Medical Research Council.
The paper on this research, CARB 81, will be presented at 9:25 a.m., Wednesday, Aug. 21, at Sheraton Boston, Republic B, during the symposium, "Carbohydrate Immunology and Therapeutics."
Peter H. Seeberger, Ph.D., is an associate professor of chemistry in the department of chemistry at Massachusetts Institute of Technology in Cambridge, Mass.
Louis Schofield, Ph.D., is a researcher at the Walter & Eliza Hall Institute of Medical Research in Melbourne, Australia.
Journal
Nature