**1. Introduction**

To date, vaccines have been able to overcome the evolution of antibiotic-resistant strains, which makes vaccination one of the most cost-effective measures for fighting infectious diseases [1]. *Mycobacterium tuberculosis* (*Mtb*) is included as 'critical' in the WHO priority list of research and development for new antibiotics effective against current resistant strains of tuberculosis (TB) [2]. Concurrently, new efficacious vaccines will be a very important tool to fight antimicrobial resistant TB (AMR TB) and are called to play an important role against this serious health issue [1].

The potential of using TB vaccines to combat AMR TB has generally been undervalued. This could be partly due to the lack of integral efficacy of the present vaccine Bacillus Calmette-Guérin (BCG) failing to reduce the numbers of TB cases, which makes new efficacious vaccines against respiratory forms of TB a critical necessity to help combat AMR TB. Currently, one of the biggest threats in TB is the emergence of multidrug-resistant (MDR) *Mtb* strains, resistant to isoniazide and rifampicin, and extensively drug-resistant (XDR) strains, resistant to at least four of the core anti-TB drugs. In 2018, half a million people were diagnosed with MDR-TB and is estimated that fifty million people were infected with MDR *Mtb* strains, creating a reservoir for future cases of active TB making treatment extremely difficult [2]. AMR poses a threat in TB; both the World Health Organization (WHO) and International Centres for Disease Control and Prevention (CDC) have expressed concern about antibiotic treatments for TB. New TB vaccines are necessary to complement existing and in-development pipeline TB treatment and diagnostic strategies. Considering there has been no evidence to suggest that molecular mechanisms of drug resistance in *Mtb* could affect immune control susceptibility, it is likely that vaccine efficacy against MDR-TB and drug-sensitive TB will be equivalent [3].

In the present work we review the current use of BCG and the non-specific effect against other pathogens and we summarized the diversity of new TB vaccine candidates in clinical trials and their indications. We discuss the need to keep the pipeline of new TB vaccine candidates and the current clinical trial designs employed in the field for efficacy determination of new TB vaccines which include designs for prevention of infection (POI), prevention of disease (POD), and prevention of recurrence of TB (POR), or trials for evaluating the therapeutic effect of TB vaccine candidates when applied in combination with current TB drug regimens with the aim to shorten duration of treatment. The pipeline includes new prime TB vaccines for administration at birth, which are expected to protect better than BCG, and for use in adolescents and adults, as revaccination strategies in individuals previously vaccinated with BCG at birth, as per WHO Preferred Product Characteristics (PPC) for new TB vaccines [3,4]. Novel TB vaccine strategies, which are safe and effective, are imperative in the global efforts to halt dissemination of drug-sensitive and AMR TB [3].
