Researchers hone in on leishmaniasis vaccine

Researchers seeking to make a vaccine against a serious parasitic infection have discovered fly saliva might be the key. A study reported in the August 6 Journal of Experimental Medicine states that scientists from the National Institute of Allergy and Infectious Diseases have developed a vaccine for a component of sand fly saliva that prevents leishmaniasis in mice.

Leishmaniasis, a disabling and sometimes deadly illness, is caused by a parasite transmitted to people and animals through the bite of a sand fly. The disease is a major health problem in many tropical and desert climates. Visceral canine leishmaniasis outbreaks were reported in North American canine populations just last year (see JAVMA, Oct. 15, 2000, page 1129). Until now, efforts to develop an effective vaccine were not promising.

"[This] report describes a novel vaccine," said NIAID Director Anthony S. Fauci, MD. "Rather than targeting the parasite, as is typical, our researchers produced a vaccine to the saliva of the insect that transmits the parasite. This approach could potentially be used to develop vaccines for other insect- or tick-borne diseases."

Leishmaniasis refers to a group of related diseases. Different species of the single-celled parasite Leishmania can cause flesh-eating nose, throat, and mouth infections; painful skin lesions; or fatal infestations of the internal organs.

According to the study, José Ribeiro, MD, of the NIAID, directed a research team that sought to use this information to produce a novel vaccine against the disease. Jesus Valenzuela, PhD, Dr. Ribeiro, and colleagues examined saliva from the sand fly carrier of Leishmania major, a parasite that causes cutaneous leishmaniasis. The researchers separated the proteins of the saliva and identified one, dubbed SP15, which appeared to be the target of natural immune responses in mice. They then worked backward, using the protein to help them find its underlying gene.

Once they identified the SP15 gene, Dr. Ribeiro's team used it to construct a DNA vaccine, which they used to vaccinate mice. When the vaccinated mice were later injected with L major parasites mixed with fly saliva, the infection was markedly milder compared with infection in mice that had not been vaccinated. The vaccinated mice had much smaller skin lesions, and their infections cleared within six weeks. Unvaccinated mice developed large skin ulcers and did not eliminate the parasite.

The results demonstrate a vaccine containing a component of sand fly saliva can protect mice from the severe signs associated with cutaneous leishmaniasis, perhaps by mimicking natural immunity to the infection.

Dr. Ribeiro next plans to test his vaccine in dogs—natural reservoirs of the parasite—and monkeys. His team also will look at other Leishmania species and the sand fly species that transmit them, hoping to develop vaccines for other forms of leishmaniasis. In addition, he has begun to study people who are naturally exposed to Leishmania to determine which components of fly saliva might protect them from disease.