• Farzad Khademi, Mohammad Derakhshan, Arshid Yousefi-Avarvand, Mohsen Tafaghodi, and Saman Soleimanpour.
• a Department of Microbiology, School of Medicine , Ardabil University of Medical Sciences , Ardabil , Iran.
• Expert Rev Vaccines. 2018 Jan 1; 17 (1): 31-44.

IntroductionMore than two billion people are latently infected with Mycobacterium tuberculosis. Most tuberculosis (TB)-subunit vaccines currently in various stages of clinical trials are designed for prevention of active TB, but not to prevent reactivation of latent TB-infection. Thus, there is an urgent need for an effective multi-stage vaccine based on early-expressed and latently-expressed antigens that prevents both acute and latent infections. Areas covered: Here, we reviewed the published pre-clinical and clinical studies of multi-stage subunit vaccines against TB, and the protective capacities of the vaccines were compared with BCG, either alone or in combination with different vaccine delivery systems/adjuvants. The results revealed that multi-stage subunit vaccines induced a wide variety of immune-responses to all forms of TB, including CD8 + T-cell-mediated cytolytic and IFN-γ responses comparable to those induced by the BCG. They could potentially be used as a booster vaccine to improve the efficacy of the BCG. Expert commentary: Multi-stage TB-vaccines could boost BCG-primed immunity, decrease bacterial loads and provide efficient protection against progressive TB-infection, especially in the latent phase. These types of vaccines administered before and after TB-infection can act as pre-exposure, post-exposure and even therapeutic vaccines. In the near future, these vaccines could provide a new generation of prime-vaccines or BCG prime-boosters.

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