Co-immunization with DNA vaccines expressing granulocyte-macrophage colony-stimulating factor and mycobacterial secreted proteins enhances T-cell immunity, but not protective efficacy against Mycobacterium tuberculosis

The development of more effective antituberculosis vaccines would assist in the control of the global problem of infection with Mycobacterium tubercul osis . One recent vaccination strategy is immunization with DNA plasmids en coding individual microbial genes. Using the genes for the M. tuberculosis- secreted proteins, MPT64 (23 000 MW) and Ag85B (30 000 MW) as candidate ant igens, we previously prepared DNA vaccines and demonstrated their ability t o stimulate T-cell responses and confer protection in a mouse model of aero sol tuberculosis (TB). The protective efficacy of the DNA vaccines was less than that promoted by the current vaccine Mycobacterium bovis bacille Calm ette-Guerin (BCG). To improve the immunogenicity and protective efficacy of these mycobacterial vectors, co-immunization of a plasmid expressing granu locyte-macrophage colony-stimulating Factor (GM-CSF) was investigated. Intr amuscular immunization with DNA expressing MPT64 or Ag85B and GM-CSF enhanc ed the antigen-specific cellular immune response, with increased proliferat ive response and production of interferon-gamma (IFN-gamma). The titre of a ntimycobacterial protein immunoglobulin G (IgG) antibodies was unchanged. M ice immunized with DNA vaccines showed reduced pulmonary bacterial load fol lowing an aerosol challenge of M. tuberculosis, but codelivery of the plasm id expressing GM-CSF did not increase the protective effect. Therefore, des pite modifying the cellular immune response to DNA vaccines, GM-CSF does no t improve their protective efficacy at the peak of infection after an aeros ol challenge with 100 c.f.u, of M. tuberculosis.