After 100 Years of BCG Immunization against Tuberculosis, What Is New and Still Outstanding for This Vaccine?

Abstract

In 2021, most of the world was reasonably still concerned about the COVID-19 pandemic, how cases were up and down in different countries, how the vaccination campaigns were ongoing, and most people were familiar with the speed with which vaccines against SARS-Co-V2 were developed, analyzed, and started to be applied in an attempt to curb the pandemic. Because of this, it may have somehow passed relatively inadvertently for people outside of the field that the vaccine used to control tuberculosis (TB), Mycobacterium bovis Bacille Calmette-Guérin (BCG), was first applied to humans a century ago. Over these years, BCG has been the vaccine applied to most human beings in the world, despite its known lack of efficacy to fully prevent respiratory TB. Several strategies have been employed in the last 20 years to produce a novel vaccine that would replace, or boost, immunity and protection elicited by BCG. In this work, to avoid potential redundancies with recently published reviews, I only aim to present my current thoughts about some of the latest findings and outstanding questions that I consider worth investigating to help develop a replacement or modified BCG in order to successfully fight TB, based on BCG itself.

Toll-like receptor-mediated innate immune responses by recognition of the recombinant dormancy-associated Mycobacterium tuberculosis proteins Rv2659c and Rv1738

“…One of recommended strategies to prevent the active TB progression in LTBI group is the vaccination [ 3 ]. However, a single approved BCG vaccine cannot induce enough immune protection against all TB stages [ 4 ]. Hence, to fulfil this gap, multi-stage subunit vaccine composing of active and latent phase antigens has been raised with the concept of stimulating the broad-immune response to both active and latent TB [ 5 ].…”

“…Vaccine is one of the potential strategies to combat this infectious stage [ 3 ]. However, a single Bacillus-Calmette-Guérin (BCG) since 1921 provides inadequate immune protection to all TB stages [ 4 ]. To fulfil this gap, a multi-stage subunit vaccine consisting of active and dormancy phase antigens has been proposed based on the idea of inducing the broad immune response against all forms of TB infection [ 5 ].…”

Recent Developments in Mycobacteria-Based Live Attenuated Vaccine Candidates for Tuberculosis

“…In addition, the product profile of an ideal therapeutic vaccine for TB is unknown. Recombinant BCG strains have received significant attention as potential replacement vaccines for BCG [ 6 , 7 , 8 ]. In contrast to subunit vaccines, live attenuated mycobacterial vaccines elicit a broader immune response and usually do not require an adjuvant.…”

Protective Efficacy of BCG Vaccine against Mycobacterium leprae and Non-Tuberculous Mycobacterial Infections

“…A topic that warrants discussion is the interaction of the BCG vaccination and the presence of NTM in the environment. The BCG vaccine is known for having lower efficacy for full protection against respiratory TB and, over the past few decades, many attempts have been made to find methods of boosting the BCG vaccine [ 33 ]. Evidence has been shown that the BCG vaccine’s efficacy is directly related to the geographical location of where the vaccine was administered and there is still much to understand regarding why exactly this is the case [ 34 ].…”