In summary, our present results showed that aerosolized boosting of γ-irradiated BCG is able to elicit Th1-biased immune responses, including antigen-specific memory CD4+ T cells concomitantly producing IFN-γ, TNF-α, and IL-2, as well as the IFN-γ response, via both the local and systemic immune systems and to eventually confer improved protection against hypervirulent Mtb HN878 infection following BCG s.c. priming and boosting. This evidence concerns the gene TNF and infection.