Protection against cutaneous Leishmaniasis resulting from bites of uninfected sand flies

Despite the fact that Leishmania are transmitted exclusively by sand flies, none of the experimental models of Leishmaniasis have established infectio n via sand fly bites. Here we describe a reproducible murine model of Leish mania major infection transmitted by Phlebotomus papatasi. Prior exposure o f mice to bites of uninfected sand flies conferred powerful protection agai nst Leishmania major that was associated with a strong delayed-type hyperse nsitivity response and with interferon-gamma production at the site of para site delivery. These results have important implications for the epidemiolo gy of cutaneous leishmaniasis and suggest a vaccination strategy against th is and possibly other vector-borne diseases.