Progressive Host-Directed Strategies to Potentiate BCG Vaccination Against Tuberculosis

Abstract

The pursuit to improve the TB control program comprising one approved vaccine, M. bovis Bacille Calmette-Guerin (BCG) has directed researchers to explore progressive approaches to halt the eternal TB pandemic. Mycobacterium tuberculosis (M.tb) was first identified as the causative agent of TB in 1882 by Dr. Robert Koch. However, TB has plagued living beings since ancient times and continues to endure as an eternal scourge ravaging even with existing chemoprophylaxis and preventive therapy. We have scientifically come a long way since then, but despite accessibility to the standard antimycobacterial antibiotics and prophylactic vaccine, almost one-fourth of humankind is infected latently with M.tb. Existing therapeutics fail to control TB, due to the upsurge of drug-resistant strains and increasing incidents of co-infections in immune-compromised individuals. Unresponsiveness to established antibiotics leaves patients with no therapeutic possibilities. Hence the search for an efficacious TB immunization strategy is a global health priority. Researchers are paving the course for efficient vaccination strategies with the radically advanced operation of core principles of protective immune responses against M.tb. In this review; we have reassessed the progression of the TB vaccination program comprising BCG immunization in children and potential stratagems to reinforce BCG-induced protection in adults.

Tuberculosis: The success tale of less explored dormant Mycobacterium tuberculosis

“…Collectively, Rpfs are suggested to be novel vaccine candidates but require further characterization and analysis to serve as a sub-unit vaccine. It is well-known that only available vaccine against TB is BCG that fails to induce long term memory and thereby insufficient to prevent resuscitation ( Negi et al., 2022 ). Therefore, a potential adjunct complex, termed as peptide-TLR agonist-liposome (PTL) when administered with BCG enhances the long-term memory and reduces the rate of reactivation, thereby reduction in bacterial burden in the lungs of mice ( Kumar et al., 2021 ).…”

Mycobacterium tuberculosis: Pathogenesis and therapeutic targets

“…Several studies have explored the potential use of Bacillus Calmette‐Guérin (BCG) as prophylaxis for TB; however, results indicate that BCG exerts suboptimal effects on immune memory. 27 , 28 , 29 Nonetheless, promising breakthroughs in the analysis of pathogen–host interactions and evolutionary investigations of Mtb offer prospective avenues for identifying pathogenicity and virulence factors that could catalyze the development of novel therapies for TB. 30 …”

Berberine governs NOTCH3/AKT signaling to enrich lung-resident memory T cells during tuberculosis

“…bovis bacille Calmette-Guérin (BCG) to prevent adult pulmonary TB makes it a requisite to employ appropriate strategies to augment the host control of M . tb infection [ 3 ].…”

“…For instance, isoniazid (INH) usage leads to the cessation of antigenresponding CD4 + T lymphocytes, which results in a heightened risk of reactivation and reinfection with M.tb [2]. Further inefficacy of the only available vaccine M. bovis bacille Calmette-Gue ´rin (BCG) to prevent adult pulmonary TB makes it a requisite to employ appropriate strategies to augment the host control of M.tb infection [3].…”