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From the * Lymphokine Regulation Unit, Laboratory of Clinical Investigation, National Institute of
Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; To determine whether DNA immunization could elicit protective immunity to Leishmania major in susceptible BALB/c mice, cDNA for the cloned Leishmania antigen LACK was inserted
into a euykaryotic expression vector downstream to the cytomegalovirus promoter. Susceptible
BALB/c mice were then vaccinated subcutaneously with LACK DNA and challenged with L. major promastigotes. We compared the protective efficacy of LACK DNA vaccination with
that of recombinant LACK protein in the presence or absence of recombinant interleukin (rIL)-12 protein. Protection induced by LACK DNA was similar to that achieved by LACK
protein and rIL-12, but superior to LACK protein without rIL-12. The immunity conferred
by LACK DNA was durable insofar as mice challenged 5 wk after vaccination were still protected, and the infection was controlled for at least 20 wk after challenge. In addition, the ability of mice to control infection at sites distant to the site of vaccination suggests that systemic
protection was achieved by LACK DNA vaccination. The control of disease progression and
parasitic burden in mice vaccinated with LACK DNA was associated with enhancement of antigen-specific interferon- Laboratory of Parasitic Diseases, National Institute for Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, Maryland 20892; § Department of Medicine, Committee on
Immunology and Gwen Kanpp Center for Lupus and Immunology Research, The University of
Chicago, Chicago, Illinois 60637; and the Institut de Pharmacologie Moléculaire et Cellulaire,
UPR411 Centre Nationale de la Recherche Scientifique, 06560 Valbonne, France
(IFN-) production. Moreover, both the enhancement of IFN-
production and the protective immune response induced by LACK DNA vaccination was IL-12 dependent. Unexpectedly, depletion of CD8+ T cells at the time of vaccination or infection
also abolished the protective response induced by LACK DNA vaccination, suggesting a role
for CD8+ T cells in DNA vaccine induced protection to L. major. Thus, DNA immunization
may offer an attractive alternative vaccination strategy against intracellular pathogens, as compared with conventional vaccination with antigens combined with adjuvants.
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