Tuberculosis Research and Scientific Applications in 2025: Advances in Diagnosis, Treatment, and Vaccines

Global Epidemiology Overview

Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex (MTBC), remains one of the world's deadliest single-pathogen infectious diseases. In 2023, approximately 10.8 million new cases were reported globally, with 1.3 million deaths, surpassing those from HIV/AIDS and COVID-19 for consecutive years.

The disease burden is heaviest in sub-Saharan Africa, Southeast Asia, and the Western Pacific, with multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB) posing ongoing challenges. Pediatric TB diagnosis lags, with over half of cases undetected. Factors like HIV co-infection, malnutrition, diabetes, smoking, and alcohol use significantly increase the risk of progression from infection to active disease.

From an immunological perspective, these high-risk groups often exhibit diminished cellular immunity, particularly IFN-γ-mediated Th1 responses, weakening the body's ability to control M. tuberculosis.

Fig. 1.Global TB Incidence and Mortality Distribution Map

Pathogen Structure and Immunological Features

The Mycobacterium tuberculosis genome spans approximately 4.4 Mb with a high GC content (around 65%), encoding roughly 4,000 genes involved in cell wall synthesis, lipid metabolism, immune evasion, and drug mechanisms. Virulence factors encoded by these genes enable bacterial survival within host cells, evasion of immune surveillance, and inflammation to promote spread. Recent studies up to 2025 highlight factors like secretion systems (e.g., ESX-1), lipids (e.g., PDIM and LAM), and stress response proteins as core targets in immunology, diagnostics, and vaccine development.

For instance, the ESX-1 system facilitates phagosome rupture, allowing bacterial escape into the cytosol, activating the NLRP3 inflammasome, and inducing necrosis to aid spread and immune evasion. Additionally, PE/PPE family proteins (e.g., PE_PGRS47) inhibit autophagy and antigen presentation, disrupting host defenses. Lipids like PDIM enhance lipid fluidity, recruit permissive monocytes, and interfere with phagosome-lysosome fusion. These mechanisms support bacterial persistence and shape granuloma dynamics, which both contain infection and provide dormancy sites. Latest advances emphasize these targets in multi-antigen vaccines, combining ESAT-6, Ag85, and TB10.4 to boost Th1 and CD8+ T cell responses.

Key Targets and Their Functions with Applications:

In-depth research into these targets reveals how M. tuberculosis manipulates host cell death pathways (e.g., ESAT-6-induced necrosis) and stress responses (e.g., KatG resisting ROS), providing foundations for more effective diagnostics (e.g., Ag85-based tests) and vaccines (e.g., multi-antigen combinations). 2025 advances include TnSeq for identifying vaccine escape genetic requirements, underscoring these factors in vaccine design.

Fig.2.Schematic of Mycobacterium tuberculosis Cell Structure and Key Antigens

Challenges in Prevention and Vaccine Development

• Diagnostic Challenges: Latent infections are asymptomatic and non-contagious but can progress to active TB at any time. TST is prone to BCG interference, reducing specificity; molecular tests like Xpert MTB/RIF Ultra offer high sensitivity close to culture methods but are limited by cost and equipment in low-income areas.
• Treatment Bottlenecks: Drug-susceptible TB requires a 6-month HRZE regimen, with poor adherence due to length; MDR-TB cure rates were only 63% in 2022. Drug toxicities (e.g., pyrazinamide, isoniazid hepatotoxicity) are limiting factors.
• Vaccine Challenges: Existing BCG offers limited protection against adult pulmonary TB, waning with age. The M72/AS01E vaccine showed ~50% reduction in TB disease risk among IGRA-positive adults in Phase IIb trials; Phase III trials completed enrollment faster than expected in 2025, with promising progress.

Fig.3.TB Prevention Pathway and Key Intervention Points

Research Application Scenarios

Aligning with current TB research priorities, key targets can be broadly applied in:

• Immunodiagnostic Development: ESAT-6/CFP-10 as core antigens for IGRA, ELISPOT, and novel immune diagnostic platforms.
• Latent Infection Mechanism Studies: HspX as a key marker for latent phase immune responses and stress tolerance research.
• Drug Resistance Mechanism Analysis: KatG and InhA as core targets for drug action studies and resistance mutation screening.
• Vaccine Target Validation: Ag85 series antigens for immune protection mechanisms and adjuvant evaluations.

Fig. 4. Applications of Different Targets in TB Research

Tuberculosis Product Catalog

Below is a list of products related to TB research, including recombinant proteins and antibodies as scientific tools:

About abinScience

abinScience is a France-based biotechnology company dedicated to advancing infectious disease research and public health solutions. We provide innovative, high-quality tools for global TB control, supporting researchers in accelerating diagnosis, treatment, and vaccine development through advanced microbiology and immunology platforms.