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Pest May Prevent Pestilence

Fly saliva may hold vaccine key, says study

TUESDAY, Aug. 7, 2001 (HealthDayNews) -- Spit from a fly sounds like an ingredient Macbeth's three witches would throw into their cauldron, but government scientists are using it to cook up their own brew to prevent deadly diseases spread by insect bites.

Proteins in the saliva of blood-sucking sand flies may be the key to a vaccine against a class of parasitic diseases, known as leishmaniasis. A report on the National Institute of Allergy and Infectious Diseases (NIAID) research is in the latest issue of the Journal of Experimental Medicine.

The research takes a different approach, comments Stephen Wikel, a University of Connecticut expert in tick-borne diseases. Instead of targeting the specific infectious agent the insects transmit, as most vaccines do, he says, "There are molecules in the [insect's] salvia that promote feeding but appear also to be essential to infection" by thinning blood, opening vessels and otherwise softening the body for an invasion. Wikel was not part of the research team.

"If you develop a vaccine that targets the individual molecules in the saliva, you can disrupt the path of transmission," says Wikel. Uncovering these molecules, chiefly proteins, might help immunologists come up with drugs that do everything from blocking clots to boosting the immune system, says Wikel, who also is trying to develop saliva-based vaccines against Lyme disease and tularemia.

But Dr. Peter Melby, a researcher at the University of Texas Health Science Center in San Antonio, who has studied leishmaniasis vaccines, says while the latest study is "very nice, what isn't clear to me is what effect this would have in the normal population."

Giving healthy people shots saliva from flies or other insects might sensitize them to bites, Melby says. "Would we all want to be hypersensitive to mosquitoes? I don't think so." On the other hand, Melby says if hypersensitivity isn't an issue, "then it's very exciting."

Leishmaniasis infections cause a range of skin-ulcerating symptoms, including mouth, skin and throat sores. The most serious and deadly variety is called visceral leishmaniasis, an organ infection that struck many Gulf War soldiers in the Middle East. If untreated, the death rate from this disease is nearly 100 percent, reports the World Health Organization.

Like malaria, the disease-causing parasite can only pass to humans through the bite of an infected insect. Species of sand flies common in nearly 90 countries worldwide can carry visceral leishmaniasis, and various types of the disease have infected about 12 million people worldwide, causing tens of thousands of deaths each year.

A number of experimental vaccines against the diseases have had little success. So far, none is on the market. Treatment with anti-parasitic drugs for more serious cases can be extremely harsh, experts say.

In the latest vaccine research, scientists at the National Institutes of Health and the Walter Reed Army Institute of Research capitalized on a long-known observation that people with a history of exposure to sand fly saliva develop a far less serious form of leishmaniasis than those who haven't had prior contact.

Led by Dr. José Ribeiro, a medical entomologist in the National Institute of Allergy and Infectious Diseases, the researchers analyzed proteins in sand fly saliva and found one, which they called SP15, that sparked a particularly strong immune response in rodents.

Ribeiro's group isolated the gene for SP15, and from it built a vaccine, which they mixed with a combination of fly saliva and Leishmaniasis major parasites, which cause skin sores. They injected the mixture into mice.

The researchers say the vaccinated animals had a much milder reaction to the microbes than their non-immunized cage mates, developing smaller ulcers that cleared within six weeks. Mice that didn't get the vaccine had larger sores and were unable to get rid of the parasite on their own. Further tests showed that the vaccine protection appeared to come from the animal's T-cells, which attack invading microbes, rather than a flood of antibodies against the parasite's DNA.

The vaccine could work as well in people as it does in mice, Ribeiro says. He and his colleagues plan to test their vaccine on dogs in France, where canine leishmaniasis is a big problem. A monkey study by scientists at Walter Reed also is in the works.

Because there are many species of sand flies and several varieties of parasites, Ribeiro says at least four or five vaccines likely will be required to cover most forms of leishmaniasis. Thanks to high-powered computers, finding the right genes and proteins now only takes about three months, he says.

Immunization would most useful to people in the developing world, particularly in countries such as the Sudan and India, where mortality rates from the parasites are high. It might also help those who travel to areas where the infection is rampant. "Anybody that would go to an exposed area could benefit in theory," Ribeiro says.

What To Do: To learn more about leishmaniasis, try the World Health Organization or the Centers for Disease Control and Prevention.

SOURCES: Interviews with José Ribeiro, M.D., Ph.D., medical entomologist, National Institute of Allergy and Infectious Diseases, Bethesda, Md.; Stephen Wikel, Ph.D., professor of physiology, Center for Microbial Pathogenesis, University of Connecticut Health Center, Farmington; Peter Melby, M.D., associate professor, University of Texas Health Science Center, San Antonio, Texas; Aug. 6, 2001 Journal of Experimental Medicine
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