Updated July 2026. Therapeutic TB vaccines are given alongside antibiotics to shorten treatment, reduce relapse, or protect against reinfection. M72/AS01E (GSK/Gates MRI) — a leading preventive candidate — also being explored therapeutically; its preventive Phase 3 completed enrollment (~20,080 participants) in 2025. DAR-901 (whole-cell heat-inactivated Mycobacterium obuense) — Phase 2b DAR-PRO trial ongoing in tuberculin skin test-positive adolescents. ID93 + GLA-SE (Access to Advanced Health Institute) — Phase 2a completed in Korea in tuberculosis-treated patients; safety and immunogenicity acceptable, effect on recurrence pending. VPM1002 (Serum Institute of India recombinant BCG) — Phase 3 in ~2,000 TB patients evaluating relapse prevention post-treatment, results expected 2026. MTBVAC (Biofabri, live attenuated M. tuberculosis) — Phase 3 preventive trial launched 2025 in South Africa and Madagascar.

Comprehensive tracking of tuberculosis (TB) therapeutic vaccine development as treatment adjunct for active TB disease, latent TB infection prevention, and drug-resistant TB immunotherapy. TB affects 10.6 million people annually with 1.3 million deaths (2nd deadliest infectious disease after COVID-19), caused by Mycobacterium tuberculosis. Standard treatment: 6-9 months multidrug regimen (rifampin, isoniazid, pyrazinamide, ethambutol) with major challenges - poor adherence (50% complete treatment), drug resistance (rifampin-resistant 410,000 cases/year, MDR/XDR-TB requiring 18-24 months toxic second-line drugs), relapse rates 5-10%. Latent TB infection (LTBI) affects 25% global population (~2 billion) - asymptomatic but 5-10% lifetime risk progression to active disease. Therapeutic vaccines aim to: (1) Boost cell-mediated immunity accelerating bacterial clearance, (2) Shorten treatment duration (6 months → 3-4 months), (3) Reduce relapse rates, (4) Prevent LTBI progression to active disease, (5) Improve outcomes drug-resistant TB. Distinct from preventive BCG vaccine (newborn vaccination, limited adult efficacy). Leading candidates: M. vaccae (inactivated mycobacterium), RUTI (fragmented MTB), MIP (Mycobacterium indicus pranii), H56:IC31, ID93/GLA-SE. Complementary to TB medications and respiratory support.

⚠️ GLOBAL TB CRISIS - TREATMENT CHALLENGES:

Tuberculosis remains major global health crisis: 10.6 million new TB cases 2022 (1.3 million deaths - 2nd deadliest infectious disease), disproportionately affects low-middle income countries (95% cases - India 27%, China 7.1%, Indonesia 10%, Philippines 7%, Pakistan 5.7%). HIV-TB co-infection devastating (187,000 HIV+ TB deaths 2022, TB leading cause death HIV+ individuals). Latent TB infection (LTBI): ~2 billion people infected with dormant MTB (25% global population), no symptoms but 5-10% lifetime risk progression active TB (higher HIV+, immunosuppressed, recent infection), treatment: 3-12 months isoniazid/rifampin prevents progression 60-90% but poor completion rates. Standard TB treatment: 6 months intensive phase (2 months rifampin + isoniazid + pyrazinamide + ethambutol) followed by continuation phase (4 months rifampin + isoniazid), cure rates 85% IF completed. Major challenges: (1) Poor adherence - only 50% complete full 6-month regimen (pills daily, side effects, feeling better after 2 months but bacteria remain, stigma, access barriers), incomplete treatment → relapse + resistance; (2) Drug-resistant TB - rifampin-resistant TB (RR-TB) 410,000 cases/year (3.8% new cases, 18% previously treated), multidrug-resistant TB (MDR-TB resistant to rifampin + isoniazid) requires 18-24 months second-line drugs (fluoroquinolones, injectables - kanamycin, capreomycin) with severe toxicity (hearing loss, kidney damage, psychiatric effects, neuropathy), cure rates 60-70% MDR-TB, extensively drug-resistant TB (XDR-TB resistant to rifampin, isoniazid, fluoroquinolones, second-line injectables) cure rates <50%, new drugs (bedaquiline, delamanid, pretomanid) improving MDR/XDR outcomes but limited access; (3) Long treatment duration - 6 months minimum commitment, directly observed therapy (DOT) required (healthcare worker watches patient take pills), logistical burden, economic costs ($1,000+ even generics - lost work time, travel clinic); (4) Side effects - hepatotoxicity (isoniazid, rifampin, pyrazinamide - 5% severe hepatitis), peripheral neuropathy (isoniazid), GI upset, rash, drug interactions (rifampin potent CYP inducer - affects HIV drugs, contraceptives, anticoagulants); (5) Relapse - 5-10% relapse after successful treatment completion (bacterial persisters survive treatment, reactivate months-years later). Therapeutic vaccines offer hope: Immune boost accelerating bacterial clearance (shorten treatment), reducing relapse (eliminate persisters), preventing LTBI progression (alternative to long preventive therapy), improving MDR-TB outcomes (restore drug sensitivity, enhance antibiotic efficacy).

🫁 Tuberculosis Therapeutic Vaccine Tracker

TB Therapeutic Vaccines by Phase