Sub-unit
vaccines utilizing purified mycobacterial
proteins or
DNA vaccines induce partial protection against mycobacterial
infections. For example, immunization with
DNA vaccines expressing the gene for the immunodominant 35000 MW
protein, common to Mycobacterium avium and Mycobacterium leprae but absent from the Mycobacterium tuberculosis complex, conferred significant protection against
infection with either virulent M. avium or M. leprae in mice. However, the level of protection was equivalent to that obtained with the viable,
attenuated vaccine, Mycobacterium bovis, bacille Calmette-Guèrin (BCG). The
cytokine,
interleukin (IL)-12, is essential for priming naïve CD4+ T lymphocytes to differentiate into
interferon-gamma (IFN-gamma)-secreting T cells. We have used a novel self-splicing vector expressing both chains of murine
IL-12 to determine if plasmid
IL-12 would increase the efficacy of a
vaccine expressing the M. avium 35000 MW
protein (DNA-Av35). Co-immunization with p2AIL-12 and DNA-Av35 led to a significant increase in the number of
antigen-specific IFN-gamma secreting cells and total amount of IFN-gamma released, but a concomitant fall in the antibody response to the 35000 MW
protein. This pattern of response was associated with enhanced clearance of M. avium from the liver and spleen of coimmunized mice, and was significantly more effective than BCG or DNA-Av35. alone. Following M. avium challenge there was significant increase in the expansion of the 35000 MW
antigen-reactive T cells in the coimmunized mice. Therefore, plasmid-delivered
IL-12 acts as an effective adjuvant to increase the protective efficacy of a single
DNA vaccine against M. avium
infection above that achieved by BCG, and this strategy may improve the efficacy of
subunit vaccines against M. leprae and M.
tuberculosis.