New combination vaccine may fight malaria.

The human immune system faces a losing battle in fighting off the parasites that cause malaria. The invaders metamorphose through four different stages as they assail the body--expressing different genes and surrounding themselves with different proteins at each stage. An immune-system attack against one form leaves the others unscathed. In an effort to counter this insidious disease, researchers have constructed a vaccine that could allow the immune system to find and fight the parasite on 21 different fronts.

The need for new measures has become more urgent as malaria parasites, including the deadly Plasmodium falciparum, have developed resistance to drugs (SN: 11/29/97, p. 340). Worldwide, the incidence of malaria is increasing--the World Health Organization estimates that 300 million to 500 million people fall ill each year and as many as 3 million die.

To protect the 40 percent of the world's population living in malarial zones, a vaccine should hit P. falciparum in all its guises, says immunologist Altaf A. Lal of the Centers for Disease Control and Prevention (CDC) in Atlanta. Lal and his colleagues report their work on the new vaccine in the Feb. 16 Proceedings of the National Academy of Sciences.

"Even if you have 99 percent protection against one stage, the one or two [parasites] that escape that layer of immunity are going to cause full-blown disease," he says. The parasites enter the body through a mosquito bite, proliferate asexually in the liver, invade red blood cells, and reproduce sexually.

Studies in western Kenya have shown that if children survive to age 10 in malaria-infested areas, they build up enough varied antibodies to resist the disease's worst effects. These antibodies recognize short protein parts, or epitopes, that adorn different stages of the parasite.

Researchers led by Ya Ping Shi of CDC chose bits of P falciparum DNA that encode many of these epitopes. They created a synthetic gene by stringing together 21 fragments representing all four parasite stages.

The researchers then produced the composite protein encoded by the synthetic malaria gene and immunized rabbits with it. The rabbits produced antibodies to all stages of P falciparum. Test-tube studies showed that these antibodies fought the parasite effectively.

Next month, CDC researchers will begin testing the vaccine's efficacy in primates. Other vaccines targeting multiple stages are also in the pipeline, says Lal.

Immunologist Louis H. Miller of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., is cautious about the prospects for any single approach. "Malaria is getting worse," he says. In the 1950s, mosquitoes were felled by pesticides, and the drug chloroquine controlled malaria in people who received it. Both the insects and the disease they carry have bounced back, and the epidemic continues to grow. Future control programs will have to combine a variety of effective strategies against the disease--drug treatments, mosquito eradication, and vaccines--Miller says.