Despite decades of efforts, tuberculosis remains a global health crisis, claiming over 1.3 million lives annually. In a comprehensive review published in Molecular Biomedicine, an international team of researchers unveils groundbreaking progress in TB vaccine development and therapeutic innovations, offering hope to curb the disease’s devastating impact.

Mycobacterium_tuberculosis_in_Ziehl-Neelsen_stained_smear_of_sputum

Source: Ajay Kumar Chaurasiya

Mycobacterium tuberculosis in Ziehl-Neelsen stained smear of sputum

The study emphasizes the limitations of the century-old Bacille Calmette-Guérin (BCG) vaccine, which fails to prevent adult pulmonary TB or latent infections. To overcome this, researchers are exploring next-generation strategies, including multi-antigen vaccines and mRNA-based platforms, currently in clinical trials. Notable candidates like GamTBvac (a subunit vaccine) and viral vector-based MVATG18598 show promise in enhancing immune responses and shortening treatment regimens.

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Artificial intelligence (AI) and bioinformatics are revolutionizing TB research. Tools like AlphaFold predict protein structures with atomic precision, accelerating antigen design. “AI helps us identify hidden patterns in pathogen biology, enabling faster, smarter vaccine development,” explains Dr. Wenping Gong, senior author of the study.

Novel therapies

The review also spotlights novel therapies for drug-resistant TB, such as bedaquiline and delamanid, which target unique bacterial pathways. Host-directed therapies (HDT), which modulate human immune responses to weaken TB persistence, are emerging as complementary strategies.

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Source: Beijing Zhongke Journal Publising Co. Ltd.

This diagram illustrates the timeline and current status of various TB vaccine candidates in clinical trials, highlighting the diversity of vaccine types and their potential impact on TB prevention and treatment.

Challenges remain, including antigen diversity, diagnostic gaps, and accessibility in low-resource regions. However, over 80 TB antigens have been identified, with 12 prioritized for vaccine development. Clinical trials for inactivated vaccines like RUTI and mRNA candidates like BNT164 are underway, aiming to address both active and latent infections.

“Our goal is to translate lab discoveries into real-world solutions,” says Dr. Gong. “Combining AI, global collaboration, and innovative trial designs will be key to meeting the WHO’s 2035 TB eradication target.”

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