Leishmania parasites are transmitted to their vertebrate hosts by infected phlebotomine sand fly bites. Sand fly saliva is known to enhance Leishmania infection, while immunity to the saliva protects against infection. This invention claims nine major salivary proteins from the sand fly vector of Leishmania major, Phlebotomus papatasi, nucleic acids encoding the proteins, vaccines comprising the proteins and/or nucleic acids, and methods of producing an immune response to prevent Leshmaniasis. The inventors have shown that one of these salivary proteins was able to protect vaccinated mice challenged with parasites plus salivary gland homogenates (SGH). A DNA vaccine containing the cDNA for the same protein provided this same protection. Protection lasted at least 3 months after immunization. The vaccine produced both intense humoral and delayed-type hypersensitivity (DTH) reactions. B cell-deficient mice immunized with the plasmid vaccine successfully controlled Leishmania infection when injected with Leishmania plus SGH.