Interferon-gamma production by mononuclear cells in Bacille Calmette-Guérin-revaccinated healthy volunteers predicted long-term antimycobacterial responses in a randomized controlled trial

The Bacille Calmette-Guérin (BCG) vaccine is the only vaccine currently available for tuberculosis, and it demonstrates variable efficacy against the disease. The assessment of new vaccine strategies is hindered by the small annual probability that an infected individual will develop tuberculosis, and the lack of simple and reliable surrogate markers of protection. The frequency of cytokine-producing T cells as well as the production of IFN-γ have been disputed as surrogate markers of protection. We evaluated the evolution of these immune parameters in a population from a high burden city where BCG revaccination has been shown to result in mild protection. We found that individuals whose in vitro IFN-γ responses to mycobacterial antigens had increased by more than 3.3-fold were more likely to maintain higher responses after 1 year and to show increased expansion of IFN-γ-producing T lymphocytes than those with lower or null increase of IFN-γ.