VACCINATION WITH DNA ENCODING THE IMMUNODOMINANT LACK PARASITE ANTIGEN CONFERS PROTECTIVE IMMUNITY TO MICE INFECTED WITH LEISHMANIA-MAJOR

To determine whether DNA immunization could elicit protective immunity to Leishmania major in susceptible BALB/c mice, cDNA for the cloned L eishmania antigen LACK was inserted into a euykaryotic expression vect or 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 D NA vaccination with that of recombinant LACK protein in the presence o r absence of recombinant interleukin (rIL)-12 protein. Protection indu ced by LACK DNA was similar to that achieved by LACK protein and rIL-1 2, but superior to LACK protein without rIL-12. The immunity conferred by LACK DNA was durable insofar as mice challenged 5 wk after vaccina tion were still protected, and the infection was controlled for at lea st 20 wk after challenge. In addition, the ability of mice to control infection at sites distant to the site of vaccination suggests that sy stemic 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-ga mma (IFN-gamma) production. Moreover, both the enhancement of IFN-gamm a production and the protective immune response induced by LACK DNA va ccination was IL-12 dependent. Unexpectedly, depletion of CD8(+) T cel ls at the time of vaccination or infection also abolished the protecti ve response induced by LACK DNA vaccination, suggesting a role for CD8 (+) T cells in DNA vaccine induced protection to L. major. Thus, DNA i mmunization may offer an attractive alternative vaccination strategy a gainst intracellular pathogens, as compared with conventional vaccinat ion with antigens combined with adjuvants.