Fighting Tuberculosis: In Search of a BCG Replacement

Abstract

Tuberculosis is one of the most threatening infectious diseases and represents an important and significant reason for mortality in high-burden regions. The only licensed vaccine, BCG, is hardly capable of establishing long-term tuberculosis protection and is highly variable in its effectiveness. Even after 100 years of BCG use and research, we still cannot unequivocally answer the question of which immune correlates of protection are crucial to prevent Mycobacterium tuberculosis (Mtb) infection or the progression of the disease. The development of a new vaccine against tuberculosis arises a nontrivial scientific challenge caused by several specific features of the intracellular lifestyle of Mtb and the ability of the pathogen to manipulate host immunity. The purpose of this review is to discuss promising strategies and the possibilities of creating a new vaccine that could replace BCG and provide greater protection. The considered approaches include supplementing mycobacterial strains with immunodominant antigens and genetic engineering aimed at altering the interaction between the bacterium and the host cell, such as the exit from the phagosome. Improved new vaccine strains based on BCG and Mtb undergoing clinical evaluation are also overviewed.

Vaccines against Tuberculosis: Where Are We Now?

“…However, in the immunocompromised individuals, HIV patients, or in TB-endemic regions, the use of pathogenic M.tb strains in any form has greater risk of infection, re-infection or relapse cases. Thus, safer rBCG strains expressing one or a few mycobacterial proteins (fusion protein) as immunogens are considered suitable and safer vaccine candidates to use [ 10 , 115 ]. rBCG strains are being investigated for eliciting a wider range of CD4 + /CD8 + T cell responses and for their longevity in protecting vaccinated individuals against multidrug-resistant TB [ 118 ].…”

“…Finally, as the efficacy of the vaccine is weakened after a few years (or months) of vaccination, a booster dose is given to re-prime the vaccine and induce memory cells. The booster dose can also be given to bolster chemotherapy using an existing drug treatment [ 115 , 116 ]. The re-administration of the BCG vaccine as a booster (booster vaccination) may lead to adverse effects, especially in immunocompromised individuals, and hence it is better to develop alternative vaccine candidates for booster function [ 115 , 116 ].…”

“…The booster dose can also be given to bolster chemotherapy using an existing drug treatment [ 115 , 116 ]. The re-administration of the BCG vaccine as a booster (booster vaccination) may lead to adverse effects, especially in immunocompromised individuals, and hence it is better to develop alternative vaccine candidates for booster function [ 115 , 116 ]. Vaccine candidates such as MVA85A, Aeras-402 fall under this category.…”

Virulence Factors of Mycobacterium tuberculosis as Modulators of Cell Death Mechanisms

“…Mtb is an intracellular pathogen, mainly infecting the respiratory tract; initially, it specifically infects resident alveolar macrophages (AMs) and replicates to survive intracellularly by avoiding the host immune response [ 4 ]. The innate immune cells in the lungs are the earliest defenders; they engulf the pathogen, degrade it, and regulate inflammation, whereas adaptive immune cells, such as CD4 and CD8 T cells, engage in the defense through an antigen-specific T cell response [ 5 ].…”

Mycobacterium tuberculosis Infection: Control and Treatment

“…All this brings the task of finding original drugs with new targets and a lack of resistance to the fore, as well as the problem of timely and effective vaccination. In their review, Nadolinskaia et al pointed out that the only licensed vaccine, BCG, is unlikely to provide long-term protection against tuberculosis because it is highly variable in its effectiveness [9]. The development of a new vaccine against tuberculosis is a non-trivial scientific task, due to a number of features of the intracellular lifestyle of M. tuberculosis, as well as its ability to manipulate host immunity.…”