Insect-saliva vaccine thwarts parasite.

Fly spit may yet make its way into the medical mainstream. A new study on mice demonstrates that a vaccine based on a component of sand fly saliva can protect against leishmaniasis, an illness that infects hundreds of thousands of people each year.

Widespread in the tropics, the sometimes fatal illness produces disfiguring lesions. It's caused by a group of single-celled parasites that dwell inside tiny blood-sucking sand flies. When they pierce a person's skin, the flies inject the parasites into the bloodstream.

Once inside the body, the Leishmania parasites evade the immune system by using a bold strategy. They insert themselves into immune system cells called macrophages, which become protective hosts to the parasites rather than their executioners. So far, this strategy has also enabled the parasites to dodge the effects of a variety of would-be vaccines.

Last year, however, researchers at the National Institutes of Health (NIH) in Bethesda, Md., reported a curious finding. When injected into mice, sand fly spit conferred immunity against Leishmania.

That result could explain why many people in Leishmania-infested regions never contract the disease, says John R. David, a tropical disease expert at the Harvard School of Public Health in Boston. These people have probably been immunized by bites from Leishmania-free flies.

Now, researchers led by Jose M.C. Ribeiro of NIH have identified a component of the spit that's particularly effective as a vaccine in mice. They report their findings in the Aug. 6 JOURNAL OF EXPERIMENTAL MEDICINE.

David suspects the approach could lead to a vaccine for people. "It's very exciting," he says.

To find the specific spit component that worked as a vaccine, researchers first dissected hundreds of salivary glands from Phlebotomus papatasi, a sand fly common in Central and South America. The researchers then separated the 12 or so salivary gland proteins. Next, the team injected different proteins into separate batches of mice, which were then exposed to Leishmania parasites.

The scientists found that the protein dubbed sp15 provoked the strongest immune response. The researchers also found that injections of DNA fragments encoding sp15 produce a robust reaction. DNA vaccines can be made cheaply and are resistant to the heat common in the tropics, notes Ribeiro.

How does the spit-based vaccine work? Ribeiro and others had already demonstrated that whole spit from parasitefree flies elicits what immunologists call a cellular response--a blitzkrieg of sorts--at the bite site. The new study shows that the DNA vaccine cranks up the same response. When bitten by an infected sand fly, a vaccinated animal's immune system is primed to do battle against the spit. And, it seems, the parasite gets caught in the crossfire, says Ribeiro.

To combat leishmaniasis in people, Ribeiro anticipates vaccines tailored to the diverse types of sand flies that infest different regions. The spit-based approach might work for other insect and tick-borne diseases, such as Dengue fever.

"I don't see why it couldn't," agrees David.