Once they identified the SP15 gene, Dr. Ribeiro's team used it to construct a DNA vaccine, which they used to immunize mice. When the immunized mice were later injected with L. major parasites mixed with fly saliva, the infection was markedly milder compared to infection in mice that had not been vaccinated. The immunized 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.
Because sand fly bites produce both antibodies and T-cell responses, the researchers analyzed the mice to see which type of immune response was keeping the parasites in check. When the NIAID team vaccinated "knockout" mice, genetically engineered not to produce antibodies, the mice were still protected by the vaccine, suggesting T cells were protecting the animals from disease.
The results demonstrate a vaccine containing a component of sand fly saliva can protect mice from the severe symptoms associated with cutaneous leishmaniasis, perhaps by mimicking natural immunity to the infection. "People get bitten by infected sand flies all the time without developing leishmaniasis," says Dr. Ribeiro. "It could be that those who develop disease are merely unlucky; they are bitten by a Leishmania-carrying fly before uninfected flies have had time to naturally immunize them."
Dr. Ribeiro nex
Contact: Sam Perdue
NIH/National Institute of Allergy and Infectious Diseases