Tracking M72/AS01E, VPM1002, MTBVAC & Next-Generation TB Vaccines
Tuberculosis (TB) kills 1.3 million people annually, making it the world's deadliest infectious disease. The only licensed vaccine, BCG (Bacillus Calmette-Guérin), developed in 1921, protects infants against severe TB but provides limited protection in adults against pulmonary TB. The pipeline includes several promising candidates: M72/AS01E showed 50% efficacy in Phase 2b trials (the first TB vaccine to show significant adult protection in decades), VPM1002 (recombinant BCG) is in Phase 3 trials, and MTBVAC (live attenuated M. tuberculosis) represents a new generation of vaccines. This tracker monitors these leading candidates plus emerging approaches including therapeutic vaccines, mRNA platforms, and viral vectors targeting both prevention and treatment of latent and active TB.
Developer: Developed by Calmette and Guérin (Institut Pasteur)
Platform: Live attenuated Mycobacterium bovis
Efficacy: 70-80% protection against severe TB (meningitis, disseminated disease) in infants; variable (0-80%) protection against pulmonary TB in adults
Status: Most widely used vaccine globally (>100 million doses annually). Part of WHO Expanded Programme on Immunization (EPI). Given at birth in TB-endemic countries.
Limitations: Protection wanes over time, limited efficacy against adult pulmonary TB (the most common form), cannot be given to immunocompromised individuals (including HIV+ patients).
Usage: Despite limitations, BCG remains the only licensed TB vaccine and is critical for preventing severe childhood TB. Administered to >90% of infants in TB-endemic regions.
Developer: GlaxoSmithKline (GSK) / Gates Medical Research Institute (Gates MRI)
Platform: Subunit vaccine containing M. tuberculosis antigens (Mtb32A and Mtb39A) with AS01E adjuvant
Breakthrough: Phase 2b trial showed 50% efficacy in preventing progression from latent to active TB in adults with latent infection - the first TB vaccine to show significant adult protection in decades
Target: Adults with latent TB infection (1/4 of global population has latent TB)
Status: Phase 3 trials initiated 2023-2024 in multiple African and Asian countries. 5,000+ participants planned. Results expected 2027-2028.
Significance: If successful, would be the first new TB vaccine in 100 years and could prevent millions of TB cases by protecting those at highest risk.
Developer: Vakzine Projekt Management GmbH / Serum Institute of India
Platform: Recombinant BCG vaccine (genetically modified BCG expressing listeriolysin)
Innovation: Improved version of BCG designed to provide better protection and safer profile in HIV+ individuals
Status: Phase 3 trials in India (newborn vaccination, BCG replacement) and South Africa (HIV-exposed infants). Testing as both BCG replacement and booster.
Advantage: Can potentially be used in HIV+ populations unlike traditional BCG, addressing major gap in TB prevention.
Developer: University of Zaragoza (Spain) / Biofabri
Platform: Live attenuated M. tuberculosis (actual TB bacteria, not M. bovis like BCG)
Rationale: Using actual M. tuberculosis may induce broader, more relevant immune responses than BCG (which uses cow TB bacteria)
Status: Phase 2 trials in newborns (South Africa) and adults. Testing as both BCG replacement and booster vaccine.
Innovation: First live attenuated M. tuberculosis vaccine to reach clinical trials - represents fundamentally new approach.
Developer: Statens Serum Institut (Denmark) / Valneva
Platform: Subunit vaccine with three M. tuberculosis antigens (Ag85B, ESAT-6, Rv2660c) and IC31 adjuvant
Target: Both prevention and therapeutic use (treating latent TB infection)
Status: Phase 2 trials in South Africa and Europe testing in adolescents/adults, both as preventive and therapeutic vaccine.
Developer: Research Institute for Biological Safety Problems (Kazakhstan) / Aeras
Platform: Recombinant influenza virus vector expressing TB antigens
Innovation: Intranasal delivery - targets mucosal immunity in the lungs where TB infection begins
Status: Phase 2 trials as BCG booster. Unique needle-free, nasal spray administration.
Developer: IDRI (Infectious Disease Research Institute, Seattle)
Platform: Subunit protein vaccine (4 TB antigens) with GLA-SE adjuvant
Target: Prevention in high-risk populations and treatment of latent TB
Status: Phase 2a trial completed in South Africa showing safety and immunogenicity. Further trials planned.
Developers: BioNTech, Moderna, academic consortia
Platform: mRNA technology encoding TB antigens
Innovation: Applying successful COVID-19 mRNA platform to TB. Can encode multiple antigens and be rapidly modified.
Status: BioNTech has TB mRNA vaccine in early Phase 1. Multiple academic programs in preclinical stages.
Potential: Could overcome BCG limitations through targeted antigen selection and strong immune activation.
Developer: University of Oxford
Platform: Chimpanzee adenovirus vector (same platform as Oxford COVID vaccine) expressing Ag85A
Status: Phase 1 trials as BCG booster. Testing safety and immunogenicity in adults.
Approach: Prime with BCG, boost with viral vector to enhance and prolong protection.
Developer: Dartmouth College / Aeras
Platform: Whole-cell vaccine derived from Mycobacterium obuense
Target: BCG booster for adolescents
Status: Phase 1 safety trials. Showed promise in adolescent boosting but development slowed.
TB vaccine development faces unique challenges: M. tuberculosis can remain dormant for decades (latent TB affects 2 billion people), the bacteria has complex cell wall structures that evade immune responses, correlates of protection are poorly understood (we don't know which immune responses predict protection), and clinical trials require large populations followed for years. BCG's variable efficacy (0-80% in different populations) reflects these complexities. However, M72/AS01E's 50% efficacy breakthrough and advances in understanding TB immunology provide renewed optimism. The field is moving toward multiple vaccines for different populations: BCG replacement for newborns, boosters for adolescents, and therapeutic vaccines for latent TB.