EFFECTIVE IMMUNIZATION OF MICE AGAINST CUTANEOUS LEISHMANIASIS USING AN INTRINSICALLY ADJUVANTED SYNTHETIC LIPOPEPTIDE VACCINE

Two peptides representing predicted T-cell epitopes of gp63, a major s urface glycoprotein of the parasite Leishmania major, were used in vac cines tested in a murine model of cutaneous leishmaniasis. Either subc utaneous or intraperitoneal immunization in saline with a peptide repr esenting gp63 amino acids 467-482 (p467) significantly protected CBA m ice against the development of severe cutaneous lesions only when the peptide was intrinsically adjuvanted by covalently adding a lauryl-cys teine moiety (LC-p467) to its amino terminus during synthesis. In mark ed contrast, administration of p467 alone, cysteinyl-p467 or gp63 prot ein in saline resulted in some disease exacerbation. Splenic cells of LC-p467 immunized mice stimulated in vitro with LC-p467 displayed stro ng proliferative responses and secretion of IL-2, IFN-tau and GM-CSF ( but not IL-4 and IL-10) suggesting that immunization with the lipopept ide induced the THl type cytokine responses associated with cell-media ted immunity. The safety, efficacy, ease of production and standardiza tion of such lipopeptide vaccines suggest that they have significant p otential for the development of vaccines for humans against leishmania sis or other parasitic or viral diseases that require cell-mediated im munity for protection. Copyright (C) 1996 Elsevier Science Ltd.