Developing an effective anti tuberculosis (TB) vaccine is a top priority for global control of TB. Since BCG has limited protection against Mycobacterium tuberculosis (MTB) infection, efforts are being made to improve its protective efficacy further. Prime-boost is a strategy whereby an individual is primed with BCG followed by boosting with a heterologous anti TB vaccine/antigen. In several instances, boosting involves up-modulation of CD4+ Th1 mediated cellular immunity by stimulation with the corresponding antigen(s) as well as by down modulating the immunosuppressive regulatory T cells. In a recent trial with such a booster candidate vaccine (MVA85A) against TB, despite enhancing the IFN-γ+CD4+Th1 mediated immunity, no significant improvement in protective efficacy against TB was observed in the vaccinated group. A possible cause for under performance of this vaccine could be the lack of killing of MTB by invaded antigen presenting cells (APCs) such as macrophages and dendritic cells (either due to MTB itself or due to polymorphisms in interferon-γ receptors). Consequently, MTB would survive and multiply inside APCs and would lead to the development of TB reflecting the non-efficacy of the vaccine. In this communication, a concise description about the probable reasons for poor performance of MVA85A in providing protection against TB has been put forth.