Web Extra: Gunning for Malaria

Author: John Monczunski

The malaria parasite, spread by female Anopheles mosquitoes, invades blood cells, multiplies, and eventually explodes the cells. This releases toxins and debris into the bloodstream, which causes the disease’s signature symptoms of intense fever followed by profuse sweating and violent chills. Each year up to 500 million cases of malaria are diagnosed worldwide, with as many as three million people dying. Most victims are pregnant women and children in Third World countries.

One way to stop the epidemic is to stop the invasion. And John H. Adams of Notre Dame’s Center for Tropical Disease Research and Training is on to something which may do just that. Not long ago Adams identified a protein made by the parasite that works like the grappling hooks of a pirate boarding party. Dubbed MAEBL, the protein is involved in binding the parasite to a person’s red blood cell wall and initiating the invasion. Because of its potential use in a malaria vaccine Adams was awarded a U.S. patent for the protein.

Currently, the associate professor of biological sciences is investigating in greater detail how MAEBL works and interacts with other molecules. “We have defined binding characteristics for MAEBL, and now we are in the process of trying to modify amino acids [in the protein] and hopefully change its ability to bind,” Adams says.

Notre Dame researchers were surprised this year to learn that MAEBL also appears at an earlier stage of infection. Before invading blood cells, the parasite first migrates to the liver, where it changes form. Team members were astonished when they found MAEBL at this liver stage of the disease. “It has become an even more interesting molecule,” Adams says. “Even though it is the same protein, it is processed differently, so, in a real sense, it’s not the same protein.”

Meanwhile, using information garnered from Adams and his Notre Dame colleagues, collaborators at the University of Michigan and the Naval Medical Research Center are testing prototype vaccines on primates and rodents. Preliminary results have been positive; the vaccine components have induced antibody responses in the animals.

Adams is hopeful but cautious about the possibilities of a MAEBL malaria vaccine.

“Part of the problem,” he says, “is that MAEBL is one of a family of similar proteins, and the parasite has redundancy built in. So it has choices as to which invasion pathway to use, and we don’t understand how it can change pathways. Those are the sorts of things we’re trying to figure out.”

John Monczunski is an associate editor for this magazine.