An Overview of the Development of New Vaccines for Tuberculosis

Abstract

Currently, there is only one licensed vaccine against tuberculosis (TB), the Bacillus Calmette–Guérin (BCG). Despite its protective efficacy against TB in children, BCG has failed to protect adults against pulmonary TB, lacks therapeutic value, and causes complications in immunocompromised individuals. Furthermore, it compromises the use of antigens present in the purified protein derivate of Mycobacterium tuberculosis in the diagnosis of TB. Many approaches, e.g., whole-cell organisms, subunit, and recombinant vaccines are currently being explored for safer and more efficacious TB vaccines than BCG. These approaches have been successful in developing a large number of vaccine candidates included in the TB vaccine pipeline and are at different stages of clinical trials in humans. This paper discusses current vaccination strategies, provides directions for the possible routes towards the development of new TB vaccines and highlights recent findings. The efforts for improved TB vaccines may lead to new licensed vaccines capable of replacing/supplementing BCG and conferring therapeutic value in patients with active/latent TB.

The emerging role of exosomal miRNAs as a diagnostic and therapeutic biomarker in Mycobacterium tuberculosis infection

“…Various of them are being in BCG, too, cause antigenic cross-reactivity and inducing a high degree of false positivity (Kasempimolporn et al 2019 ). A reduction in the antigen cross-reactivity is needed for test precision, despite the limited investigation and discussions that have marked this dilemma (Whitlow et al 2020 ).…”

Immunological Characterization of Proteins Expressed by Genes Located in Mycobacterium tuberculosis-Specific Genomic Regions Encoding the ESAT6-like Proteins

“…Two other subunit vaccine candidates which have undergone clinical trials in humans are H1:IC31 and H56:IC31 [ 190 , 191 ]. The subunit vaccine H1:IC31 contains a fusion of Ag85B and ESAT6 and is given along with the adjuvant IC31 [ 192 , 193 ].…”

“…A phase 1b randomized study with the H56:IC31 vaccine showed that the vaccine had acceptable safety profiles in M. tuberculosis -uninfected adults and induced immunizing antigen-specific cellular and humoral immune responses [ 204 ]. This vaccine candidate is now being tested in phase 2a clinical trials, and recruitment has started for the phase 2b clinical trial [ 190 ].…”

“…The ID93/GLA-SE vaccine enhanced the magnitude and polyfunctional cytokine profile of CD4 + T cells, as compared to ID93 alone [ 221 ]. This vaccine is currently being tested in a phase 2 clinical trial [ 190 ].…”

Where are the RNA vaccines for TB?

“…The view that adequate protection against bacterial infections such as TB will require delivery of a complexity of diverse antigens by virulence-attenuated vectors such as live BCG or attenuated M. tuberculosis has not been discounted; current understanding of the requirements for generating protective immunity is limited [ 9 ] and multiple forms of vaccine are being investigated [ 10 ], and must continue to be investigated. However, the attainment of potent protection with a limited number of TB antigens (subunits) remains a realistic ambition that has precedents in animal models of TB [ 11 , 12 ] and a range of subunit candidate vaccines are in clinical trials [ 9 , 10 ]. The ivt RNA approach may be ideally suited for the subunit approach.…”