INDUCTION OF A TH1 IMMUNE-RESPONSE AND SIMULTANEOUS LACK OF ACTIVATION OF A TH2 RESPONSE ARE REQUIRED FOR GENERATION OF IMMUNITY TO LEISHMANIASIS

Experimental systems based on immunization with plasmid DNA or immune- stimulating complexes were used to delineate the requirements for gene ration of protective immunity against murine leishmaniasis. Vaccinatio n with plasmid DNA encoding the host-protective Leishmania major paras ite surface Ag-2 primed for an essentially exclusive Th1 response that protected mice against L, major infection, In contrast, parasite surf ace Ag-2 in immune-stimulating complexes generated an immune response with mixed Th1-like and Th2-like properties that was not protective de spite the activation of large numbers of CD4(+) T cells secreting IFN- gamma, These results indicate that a Th1 response is sufficient to pro tect against cutaneous leishmaniasis, but the induction of a simultane ous Th2 response abrogates the Th1 effector function, DNA vaccines may therefore have an advantage for diseases in which protection depends on the induction of Th1 responses.