While all the above DNA vaccines were based on Leishmania antigens, an alternative approach has used antigens derived from sand-fly saliva. Indeed, it has been shown that sand-fly saliva can exacerbate Leishmania infection [68, 69] , and preexposure of mice to saliva components may be sufficient to induce protection against infection [70] . Thus, a number of salivary antigens have been tested as vaccines against Leishmania. Maxadilan is a potent vasodilator from sand-fly saliva and was found to be responsible of most of the exacerbatory effects of whole saliva on Leishmania infection [71] . Immunization with this antigen (as a recombinant vaccine) protected mice against L. major infection [71] . Other salivary components, such as Phlebotomus papatasi SP15, have been tested as DNA vaccines and found to protect mice against L. major and while the vaccine induced both humoral and DTH responses, protection seemed to be mostly accounted for by the latter, as B-cell deficient mice remain protected [72] . Thus, characterization of sand-fly salivary proteins may lead to the identification of new vaccine candidates [73, 74] . However, as for Leishmania antigens, salivary protein polymorphism remains an important issue and may limit the usefulness of such antigens as vaccine candidates [75, 76] .