Toward a defined anti-Leishmania vaccine targeting vector antigens: Characterization of a protective salivary protein

Lcislunania parasites are transmitted to their vertebrate hosts by infected phlebotomine sand fly bites. Sand fly saliva is known to enhance Leisliman ia infection, while immunity to the saliva protects against infection as de termined by coinoculation of parasites with vector salivary gland homogenat es (SGHs) or by infected sand fly bites (Kamhawi, S., Y. Belkaid, G. Modi, E. Rowton, and D. Sacks. 2000. Science. 290:1351-1354). We have now charact erized nine salivary proteins of Phlebotomus papatasi, the vector of Leishm ania major. One of these salivary proteins, extracted from SDS gels and hav ing an apparent mol wt of 15 kD, was able to protect vaccinated mice challe nged with parasites plus SGH. A DNA vaccine containing the cDNA for the pre dominant 15-kD protein (named SP15) provided this same protection. Protecti on lasted at least 3 ino after immunization. The vaccine produced both inte nse humoral and delayed-type hypersensitivity (DTH) reactions. B cell-defic ient mice immunized with the SP15 plasmid vaccine successfully controlled L eislimania infection when injected with Leislimania plus SGH. These results indicate that DTH response against saliva provides most or all of the prot ective effects of this vaccine and that salivary gland proteins or their cD NAs are viable vaccine targets against leishmaniasis.