Protective effect of DNA immunization against mycobacterial infection is associated with the early emergence of interferon-gamma (IFN-gamma)-secreting lymphocytes

The development of more effective anti-tuberculosis (TB) vaccines would con tribute to the global control of TB. Understanding the activated/memory T c ell response to mycobacterial infection and identifying immunological corre lates of protective immunity will facilitate the design and assessment of n ew candidate vaccines. Therefore, we investigated the kinetics of the CD4() T cell response and IFN-gamma production in an intravenous challenge mode l of Mycobacterium bovis bacille Calmette-Guerin (BCG) before and after DNA immunization. Activated/memory CD4(+) T cells, defined as CD44(hi)CD45RB(l o) expanded following infection, peaking at 3-4 weeks, and decreased as the bacterial load fell. Activated/memory CD4(+) T cells were the major source of IFN-gamma and the level of antigen-specific IFN-gamma-secreting lymphoc ytes, detected by ELISPOT, paralleled the changes in bacterial load. To exa mine the effects of a DNA vaccine, we immunized mice with a plasmid express ing the mycobacterial secreted antigen 85B (Ag85B). This led to a significa nt reduction in mycobacteria in the liver, spleen and lung. This protective effect was associated with the rapid emergence of antigen-specific IFN-gam ma-secreting lymphocytes which were detected earlier, at day 4, and at high er levels than in infected animals immunized with a control vector. This ea rly and increased response of IFN-gamma-secreting T cells may serve as a co rrelate of protective immunity for anti-TB vaccines.