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

The development of more effective anti‐tuberculosis (TB) vaccines would contribute to the global control of TB. Understanding the activated/memory T cell response to mycobacterial infection and identifying immunological correlates of protective immunity will facilitate the design and assessment of new candidate vaccines. Therefore, we investigated the kinetics of the CD4+ T cell response and IFN‐γ production in an intravenous challenge model of Mycobacterium bovis bacille Calmette–Guérin (BCG) before and after DNA immunization. Activated/memory CD4+ T cells, defined as CD44hiCD45RBlo, 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‐γ and the level of antigen‐specific IFN‐γ‐secreting lymphocytes, detected by ELISPOT, paralleled the changes in bacterial load. To examine the effects of a DNA vaccine, we immunized mice with a plasmid expressing the mycobacterial secreted antigen 85B (Ag85B). This led to a significant reduction in mycobacteria in the liver, spleen and lung. This protective effect was associated with the rapid emergence of antigen‐specific IFN‐γ‐secreting lymphocytes which were detected earlier, at day 4, and at higher levels than in infected animals immunized with a control vector. This early and increased response of IFN‐γ‐secreting T cells may serve as a correlate of protective immunity for anti‐TB vaccines.

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