Synthetic protein may yield malaria vaccine.

A lab-made version of a protein found on the parasite that causes most serious cases of malaria elicits a potent immune response when given to people, suggesting it could become the basis of a vaccine against the disease.

No malaria vaccine has yet proved practical in people, and this new approach remains a long shot. Still, the synthetic-protein fragment offers hope because it spurs production of both antibodies and immune cells, scientists report in the July EUROPEAN JOURNAL OF IMMUNOLOGY. The fragment is patterned after a portion of a malaria protein called circumsporozoite.

Malaria strikes roughly 500 million people worldwide every year and kills 3.5 million of them.

Over a 6-month period, the researchers gave 16 volunteers who had never lived in a malarial zone three injections each of the new vaccine.

In every participant, the vaccine engendered antibodies against circumsporozoite and whipped up an army of immune system warriors called CD4 and CD8 T cells, says study coauthor Giampietro Corradin, a biochemist at the University of Lausanne in Epalinges, Switzerland. His laboratory developed the vaccine. Corradin and his colleagues also tested eight of the volunteers for interferon gamma, a protein made by T cells that orchestrates immune responses. In six of them, the vaccine boosted concentrations of interferon gamma, boding well for the vaccine.

Scientists have induced CD8 T cell responses against malaria, but only by using DNA- or virus-based vaccines. DNA vaccines are still untested in people, and virus vaccines have raised safety concerns. The new vaccine caused no serious side effects in the volunteers.

T cell responses to the synthetic-protein fragment make this "a very important study," says Walter R. Weiss, an immunologist at the Naval Medical Research Center in Silver Spring, Md. Weiss says that many malaria researchers consider T cells essential to stopping malaria, because these cells can get at the parasite as it hides inside liver cells, whereas antibodies can't.

The blood concentrations of antibodies induced by the synthetic vaccine were as high or higher than levels in blood from people of Burkina Faso, Mali, and Colombia--all endemic malarial zones--who had donated blood samples. Corradin says he plans eventually to vaccinate people in areas where malaria is endemic to test the vaccine's true worth.

The circumsporozoite protein covers the sporozoite--the nascent stage of Plasmodium falciparum, which is the protozoan that causes malaria. Anopheles mosquitoes carry sporozoites and inject them into people. Once in the blood stream, the sporozoites lodge in the liver and develop into the parasite.

"This [protein] fragment is important for the attachment of sporozoites to liver cells," says Corradin. "Antibodies specific for this fragment could inhibit sporozoite invasion."

This is the first malaria vaccine to elicit CD4, CD8, and antibody responses in people, he says.