Revisiting the Heterogeneous IFN-γ Response of Bacille of Calmette-Guérin (BCG)-Revaccinated Healthy Volunteers in a Randomized Controlled Trial: Effect of the Body Mass Index and of the IFNG+874 A/T Polymorphism.

In trials evaluating the immune responses to Bacille of Calmette-Guérin (BCG), the genetic background and the nutritional status are host-related factors that could affect the heterogeneity in these parameters. The IFNG+874 A/T (rs 62559044) polymorphism has been reported to influence the IFN-γ production by BCG-vaccinated individuals challenged in vitro with mycobacterial antigens. The body mass index (BMI) is a proxy for the nutritional status and has been associated both with the susceptibility to tuberculosis and with the IFN-γ response. We show that although the IFNG+874 A/T polymorphism was not associated with the heterogeneity of IFN-γ production in a randomized controlled trial that evaluated long-term immune responses to BCG revaccination previously conducted in Salvador, Bahia, Brazil, the effect of this polymorphism on the observed increase in IFN-γ production among revaccinated subjects was adjusted in individuals with a low BMI.

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.