Protective immune responses induced by vaccination with an expression genomic library of Leishmania major

To develop an effective vaccine against the intracellular protozoan parasit e Leishmania spp,, we investigated the feasibility of expression library im munization (ELI) in the mouse. Genomic expression libraries of L, major wer e constructed and used to immunize mice. One of the three libraries (L1, wi th 10(5) clones) induced a significant protective immune response and delay ed the onset of lesion development in highly susceptible BALB/c mice after i.m. immunization, compared with control mice immunized with the empty vect or (EV), L1 was then divided into five sublibraries of similar to 2 x 10(4) clones each. Mice immunized with one of the sublibraries (SL1A) developed an even stronger protective effect than that induced by L1, SL1A was furthe r divided into 20 sublibraries (SL2) of similar to 10(3) clones each. One o f the SL2 libraries (SL2G) induced a strong protective effect against L, ma jor infection, In direct comparative studies, the protective effect of the sublibraries was in the order of SL2G > SL1A > L1, Lymphoid cells from mice vaccinated with SL2G produced more IFN-gamma and NO, compared with cells f rom control mice injected with EV, Serum from the vaccinated mice also cont ained more parasite-specific IgG2a Ab, compared with controls. Therefore, t hese data demonstrate that ELI is feasible against this complex intracellul ar parasitic infection, by preferentially inducing the development of Th1 r esponses. Furthermore, by sequential division of the libraries, this approa ch may be used to enrich and identify protective genes for effective gene v accination against other parasitic infections.