Two-pronged vaccine blocks malaria.

When it comes to malaria vaccines, two may be better than one, according to a new study in mice.

A vaccination containing two proteins from the surface of the early-stage malaria parasite completely protects mice from the disease, reports a research team from Bethesda, Md. The experiment marks the first time a protein vaccine has completely prevented malaria infection in vivo, says Stephen L. Hoffman of the Naval Medical Research Institute, who conducted the work with colleagues there and at the National Institute of Allergy and Infectious Diseases (NIAID).

The findings, described in the May 3 SCIENCE, could shift the focus of malaria research away from vaccines based on a single type of protein and toward those based on multiprotein "cocktails."

At present, physicians have no effective vaccine for this mosquito-borne disease, which kills more than 2.5 million of the 270 million people it strikes each year. In human trials, test vaccines incorporating only one type of protein from the malaria parasite have protected only half of those immunized (SN: 3/26/88, p.202). The quest for a reliable vaccine has intensified as a growing proportion of Plasmodium falciparum -- the malaria organism that most often causes death -- has grown resistant to antimalarial drugs.

The new two-protein vaccine blocks the first stage in the parasite's life cycle -- the sporozoite, which mosquitoes inject as they suck blood. Sporozoites travel through the bloodstream to the liver, where each can divide into thousands of merozoites. A week later, the merozoites leave the liver to invade red blood cells. The fever, chills and aches of malaria result when infected red cells explode, releasing more merozoites. Other red cells release gametocytes, the parasite's sex cells. The life cycle comes full circle when a mosquito withdraws the gametocytes in a blood meal and they combine in the insect to produce new sporozoites.

Hoffman's team injected 18 mice with mouse tumor cells engineered to contain the genes for two proteins found on the sporozoite surface. The researchers anticipated that the tumor cells would manufacture the sporozoite proteins and display them along with their own immunity-stimulating surface proteins, thereby boosting the immune reactions of the mice. Indeed, none of the immunized mice developed malaria infection, even when injected with more than 10 times the number of sporozoites known to cause malaria in mice. In contrast, when the team injected two groups of mice with tumor cells that produce only one of the sporozoite proteins, only 33 to 75 percent escaped the infection.

"This vaccine might prevent the blood stage [of malaria] from ever occurring," Hoffman told SCIENCE NEWS. But he cautions that the Plasmodium species that cause malaria in mice differ from those infecting humans. He and his co-workers are now working to isolate. P. falciparum sporozoite proteins that parallel those used in the mouse vaccine.

Louis H. Miller of NIAID, who was not involved in the study, notes that Hoffman's group must find another way to give such a vaccine to humans. "Obviously you can't give cancer cells to patients," he says.