From antigens to immune responses: Shaping the future of TB detection and prevention

Abstract Tuberculosis (TB) remains a global health challenge due to various factors, including delayed diagnoses leading to the spread of infection, limited efficacy of current vaccination strategies, and emergence of drug-resistant strains. In this review, we explore the significance of Mycobacterium tuberculosis (Mtb)-specific antigens to overcome these challenges. We discuss a variety of antigens expressed at different stages of Mtb infection and associated T cell functional heterogeneity to its diverse antigenic landscape. Additionally, we highlight essential considerations when evaluating the immunogenicity of antigens for potential translational applications. Factors such as magnitude of memory response, cytokine profile, immunodominance, and conservation of epitopes should be emphasized as crucial parameters in assessing the potential efficacy of these antigens in diagnostics or vaccine research. Further, we cover methods used for the identification and characterization of antigens/epitopes within the context of TB with recent advances in high-coverage genomic and proteomic approaches. Recognizing the antigenic repertoire of Mtb changes with the infection stage, we highlight the importance of assessing the availability of different subsets of Mtb antigens across the spectrum of infection for more precise disease classifications. Targeting specific antigens holds promise as a pathway for developing specific immunological biomarkers to predict TB reactivation in populations.