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*
Department of Immunology, University of Glasgow, Glasgow, United Kingdom; and
Molecular Biology and Immunology Division, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
To develop an effective vaccine against the intracellular protozoan
parasite Leishmania spp., we investigated
the feasibility of expression library immunization (ELI) in the mouse.
Genomic expression libraries of L. major were
constructed and used to immunize mice. One of the three libraries (L1,
with 105 clones) induced a significant protective immune
response and delayed the onset of lesion development in highly
susceptible BALB/c mice after i.m. immunization, compared with control
mice immunized with the empty vector (EV). L1 was then divided into
five sublibraries of 
2 x 104 clones each. Mice
immunized with one of the sublibraries (SL1A) developed an even
stronger protective effect than that induced by L1. SL1A was further
divided into 20 sublibraries (SL2) of 103 clones each.
One of the SL2 libraries (SL2G) induced a strong protective effect
against L. major 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-
and NO, compared with cells from control
mice injected with EV. Serum from the vaccinated mice also contained
more parasite-specific IgG2a Ab, compared with controls. Therefore,
these data demonstrate that ELI is feasible against this complex
intracellular parasitic infection, by preferentially inducing the
development of Th1 responses. Furthermore, by sequential division of
the libraries, this approach may be used to enrich and identify
protective genes for effective gene vaccination against other parasitic
infections.
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