Host-Pathogen Interactions and Immunological Targets for Tuberculosis Vaccine Development: A Review

Abstract

Tuberculosis (TB), caused by the bacillus Mycobacterium tuberculosis (Mtb), remains a formidable global health challenge, responsible for millions of annual death toll. Despite the widespread deployment of the Bacillus Calmette-Guérin (BCG) vaccine, its limited efficacy in preventing pulmonary TB in adults, coupled with the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, necessitates the development of a more effective vaccine. This review explores the complex host-pathogen interactions that define Mtb infection, highlighting the bacterium's immune evasion strategies. These strategies include inhibiting phagosome-lysosome fusion, modulating antigen presentation, and suppressing pro-inflammatory cytokine responses. A key pathological feature of TB is the formation of granulomas, which function as both a containment mechanism and a survival niche for the bacterium. By providing an overview of these intricate mechanisms, this paper identifies and discusses promising immunological targets for next-generation TB vaccines, such as ESAT-6, the Ag85 complex, and PPE proteins. A deeper understanding of these host-pathogen dynamics is essential for designing durable and effective vaccine candidates to mitigate the global burden of TB.