GSK692342 / GSK, Bill & Melinda Gates Foundation - LARVOL DELTA

Where we are in the TB vaccine pipeline: candidates, platforms and timelines (ERS 2026) - "State-of-the-art walk-through of the clinical pipeline: adjuvanted protein vaccines (M72/AS01E), live-attenuated (MTBVAC), vectored vaccines, and emerging mRNA platforms; what the phase III/late-stage trials are testing, endpoints, and expected timelines. Collaboration with TBVI, IAVI and funders and the likely regulatory path"

Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Genetic characterization of M. tuberculosis isolates from participants in a Phase 2b randomized trial evaluating the M72/AS01E tuberculosis candidate vaccine. (PubMed, J Infect Dis) - P2 | "This descriptive analysis showed no apparent preferential distribution of local M. tuberculosis strains in M72/AS01E or placebo recipients. These results support the continued development of this candidate vaccine."

Journal • P2b data • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Advances in development of tuberculosis vaccines and preventive drug therapies: current pipeline, evidence, and access. (PubMed, Lancet Microbe) - "Platforms include live-attenuated mycobacterial vaccines (eg, MTBVAC), recombinant BCG-derived approaches (eg, VPM1002), protein-adjuvant subunit vaccines (eg, M72/AS01E), viral-vectored candidates (eg, AdHu5Ag85A, ChAdOx1.85A, and TB/FLU-04L), and inactivated whole-cell strategies (eg, DAR-901, RUTI, and Immuvac [MIP])...For contacts of multidrug-resistant or rifampicin-resistant tuberculosis, randomised trials and pooled analyses support 6 months of daily levofloxacin to reduce incident multidrug-resistant tuberculosis. Bedaquiline-containing preventive regimens and shorter fluoroquinolone-based combinations are under clinical evaluation, but definitive phase 3 efficacy data are not yet available. The expansion of the vaccine pipeline alongside improved short-course preventive regimens offers a credible opportunity to accelerate tuberculosis incidence decline, although translation into population-level impact will depend on shown efficacy, sustained financing, reliable..."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Immunotherapy for tuberculosis: current landscape, mechanistic insights, and translational perspectives. (PubMed, Front Immunol) - "This review integrates recent advances across the immunotherapy landscape, including next-generation vaccines (M72/AS01E, MTBVAC, VPM1002, BNT164 mRNA candidates), host-directed therapies (HDTs) targeting autophagy, metabolic and inflammatory pathways, cytokine-based and antimicrobial peptide strategies, and adoptive cell therapies. Key translational challenges-the absence of reliable correlates of protection, the demand for precision immunomodulation in comorbid populations (HIV, diabetes), and chronic underfunding of TB research-are discussed alongside emerging opportunities offered by mRNA platforms, repurposed drugs, and multi-omics-guided patient stratification. Collectively, immunotherapy is evolving from an adjunctive concept into a strategic pillar of TB control, with the potential to shorten treatment, prevent relapse, and address drug-resistant disease."

Journal • Review • Diabetes • Human Immunodeficiency Virus • Immunology • Infectious Disease • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • Tuberculosis • PD-1 • PD-L1

Design and feasibility considerations for a phase 3 efficacy trial of the M72/AS01E-4 tuberculosis vaccine. (PubMed, Vaccine) - "An IGRA-positive-enriched, event-driven phase 3 trial is feasible to confirm VE(D) of M72/AS01E-4 while evaluating safety and immunogenicity across IGRA and HIV groups."

Journal • P3 data • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Vaccine development against Mycobacterium tuberculosis: a PRISMA-guided systematic review of conventional and computational multi-epitope approaches. (PubMed, Clin Exp Vaccine Res) - "Clinical-stage development remains dominated by conventional platforms, with M72/AS01E demonstrating 54% efficacy in a Phase 2b trial and advancing to Phase 3 evaluation, representing the most promising next-generation candidate to date...However, no computationally designed MEV has yet progressed to clinical evaluation, highlighting a significant translational gap between predictive modeling and experimental validation. TB vaccine research is increasingly transitioning toward rational, computationally guided strategies, but integration of computational discovery with rigorous preclinical and clinical validation remains essential to accelerate the development of effective next-generation TB vaccines."

Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Reinfection as a central constraint on tuberculosis vaccine development. (PubMed, Front Immunol) - "Although several candidates have advanced clinically, only M72/AS01E has demonstrated prevention of disease in adults...Under MCI conditions, BCG conferred only marginal additional protection compared with single infection. Collectively, these findings identify reinfection as a central biological constraint on prophylactic TB vaccines and support incorporating MCI models into preclinical pipelines to enhance predictive value and prioritize prevention of disease."

Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Preparing for Tuberculosis Vaccine M72/AS01E Implementation: A Global Demand Forecast and Key Influential Factors. (PubMed, Infect Dis Ther) - "M72/AS01E has the potential to reduce the TB burden worldwide. Successful vaccine introduction requires early and coordinated planning, with detailed demand forecasting refined over time. The model will be updated as new data and country implementation plans emerge. To avoid access delays, continued collaboration among key stakeholders, including vaccine suppliers, and early visibility on policy recommendations and domestic and donor funding availability will be critical in the coming years."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

TB vaccine development: monitoring international patent filings to anticipate access challenges. (PubMed, Front Public Health) - "Two vaccine candidates were selected (MTBVAC and M72/AS01E) based on their development stage and platform features. Our results show that there were patent filings in countries with existing manufacturing capacity, unveiling a corporate strategy to include those countries. The study anticipates the potential access challenges related to intellectual property barriers for expanding manufacturing capacity in middle-income countries to allow future TB vaccines to be available in a timely and equitably manner for those most in need."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Status of Tuberculosis Vaccines Development in Clinical Trials (PubMed, Jugan Geongang Gwa Jilbyeong) - "The recombinant protein-based M72/AS01E vaccine has been mentioned as a potential vaccine, and is currently recruiting subjects for a Phase 3 clinical trial. In addition, recombinant protein-based GemTBvac and whole cell-based MIP, MTBVAC, and VPM1002 are in Phase 3 clinical trials. While several platform-based TB vaccine candidates are in clinical trials; however, the antigens contained in these candidates are often redundant and limited. To diversify the TB vaccine clinical pipeline, it is necessary to continue research to identify new antigens, the development of preclinical animal models for efficacy evaluation, and the identification of valid endpoints through the analysis of clinical trial results are necessary."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Overcoming Treatment Challenges in HIV-Associated Mycobacterial Diseases: New Therapeutic Frontiers. (PubMed, Int J Mol Sci) - "Beyond established regimens, we highlight host-directed strategies such as metformin, glutathione augmentation, mTOR modulation, and vitamin D; immunotherapies including interferon-γ, GM-CSF, and IL-7; and therapeutic vaccines (M72/AS01E, MTBVAC, VPM1002) as promising adjuncts. Distinct from guideline-focused overviews, this review emphasizes non-tuberculous mycobacterial disease (NTM, including MAC) and leprosy in PLWH and synthesizes host-directed and adjunctive strategies with their translational prospects, including ART compatibility and IRIS. By integrating TB, NTM, and leprosy across the HIV care continuum, we highlight opportunities not treated in detail elsewhere-particularly HDT-enabled approaches and implementation considerations in PLWH."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CSF2 • IFNG • IL7

Progress of single-cell sequencing technology in immunotherapy for tuberculosis. (PubMed, Front Cell Infect Microbiol) - "Novel therapeutic vaccines like M72/AS01E demonstrate 54% efficacy in preventing pulmonary TB, while host-directed therapies including nano-based drug delivery systems offer enhanced treatment outcomes...This review provides a critical overview of the immunological mechanisms underlying tuberculosis, immunotherapy for tuberculosis, and single-cell sequencing technology, with specific focus on key findings from recent studies and their clinical implications. It primarily focuses on discussing the research progress of single-cell sequencing technology in the context of tuberculosis immunotherapy and identifies current challenges and future research priorities."

IO biomarker • Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Advancing the fight against tuberculosis: integrating innovation and public health in diagnosis, treatment, vaccine development, and implementation science. (PubMed, Front Med (Lausanne)) - "While innovations like the Xpert MTB/RIF Ultra, BPaLM regimen, and next-generation vaccines such as M72/AS01E represent pivotal progress, their deployment remains uneven...Eliminating TB demands more than biomedical breakthroughs-it requires a unified strategy that aligns innovation with access, equity, and sustainability. By bridging science with implementation, and integrating diagnostics, treatment, and prevention within robust health systems, the global community can accelerate the path toward ending TB."

Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Adult TB vaccine: Possible novel tool to end TB (MTS 2025) - "We will discuss the immunopathogenesis of TB and how it informs vaccine development, highlighting key vaccine candidates such as M72/AS01E, VPM1002, and BCG revaccination strategies. Furthermore, the lecture will address how adult TB vaccination could synergize with existing TB control strategies, including latent TB treatment, diagnostics, and public health interventions. Special focus will be given to implementation considerations, including population targeting, delivery logistics, and cost-effectiveness in low- and middle-income countries."

Clinical • Infectious Disease • Respiratory Diseases • Tuberculosis

Multilevel systems biology analysis identifies key immune response profiles and potential correlates of protection for M72/AS01E vaccine against tuberculosis. (PubMed, Clin Exp Vaccine Res) - "Additionally, the study pinpointed a miRNAs-transcription factors (TF)-target regulatory network excavating key TF, miRNA, mRNAs mediating vaccine protection. Our results provided new insights into M72/AS01E immunity, warranting further study to optimize and guide future TB vaccine development."

IO biomarker • Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Safety and immunogenicity of investigational tuberculosis vaccine M72/AS01E-4 in people living with HIV in South Africa: an observer-blinded, randomised, controlled, phase 2 trial. (PubMed, Lancet HIV) - P2 | "The two-dose regimen of the M72/AS01E-4 tuberculosis vaccine was immunogenic, with an acceptable safety profile. These outcomes led to the inclusion of people living with HIV in the ongoing global registration phase 3 trial."

Journal • P2 data • Dermatology • Human Immunodeficiency Virus • Infectious Disease • Pain • Pruritus • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4

The PE/PPE family proteins of Mycobacterium tuberculosis: evolution, function, and prospects for tuberculosis control. (PubMed, Front Immunol) - "Clinical progress in PE/PPE-based vaccines, such as M72/AS01E and ID93/GLA-SE, underscores their promise in combating TB, while challenges in epitope variability and functional redundancy demand innovative strategies. By integrating evolutionary, structural, and immunological insights, this review provides a roadmap for leveraging PE/PPE biology to develop next-generation TB interventions."

Journal • Review • Immune Modulation • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

PPE18 and PepA Variations in Mycobacterium tuberculosis Clinical Isolates from Makassar, Indonesia: Challenges for Immune Recognition and Vaccine Development. (PubMed, Int J Mycobacteriol) - "PPE18 genetic variation may influence immune recognition and the effectiveness of M72/AS01E. Ongoing antigenic surveillance in endemic areas is essential to guide vaccine design and diagnostics."

IO biomarker • Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • IL10 • TLR2

Study to Assess Efficacy and Safety of M72/AS01E-4 Mycobacterium Tuberculosis (Mtb) Vaccine in Adolescents and Adults (clinicaltrials.gov) - P3 | N=20081 | Active, not recruiting | Sponsor: Bill & Melinda Gates Medical Research Institute | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

The critical role of new tuberculosis vaccines in achieving the WHO 2035 End TB target. (PubMed, IJID Reg) - "Although advancements in vaccine research, including candidates such as M72/AS01E, show promise, the article underscores that achieving TB elimination requires vaccines that can prevent TB infection reactivation and transmission of drug-resistant strains. Overcoming scientific, logistical, and distribution challenges, particularly, in high-burden regions, will be critical to accelerating the availability of these vaccines. The article calls for intensified global collaboration and sustained investment in research to accelerate the development of novel vaccines, which are indispensable for reaching the World Health Organization's ambitious 2035 TB elimination targets."

Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Estimating the potential health and economic impacts of new tuberculosis vaccines under varying delivery strategies in Delhi and Gujarat, India: a modelling study. (PubMed, Lancet Reg Health Southeast Asia) - "We used modelling to simulate hypothetical scenarios of introducing M72/AS01E (with 50% efficacy to prevent disease) and BCG-revaccination (with 45% efficacy to prevent infection) in Delhi and Gujarat...Additional trials for both vaccines are underway, which will provide further evidence on the vaccine efficacy and narrow the range of uncertainty on the estimates. Bill & Melinda Gates Foundation (INV-001754)."

HEOR • Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Optimising the M72/AS01E tuberculosis vaccine candidate phase 3 trial based on the phase 2b trial results. (PubMed, Vaccine) - No abstract available

Journal • P2b data • P3 data • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Tuberculosis: An Update for the Clinician. (PubMed, Respirology) - "Encouraging clinical results have been seen with the M72/AS01E vaccine...New shorter, all-oral treatment regimens represent a breakthrough, but progress is threatened by rising resistance to bedaquiline...Post-TB lung disease (PTLD) is an under-recognised but growing concern, affecting millions of survivors with lasting respiratory impairment and increased mortality. Continued investment in development of TB vaccines and therapeutics, treatment shortening, and management of TB sequelae is critical to combat this ongoing public health challenge."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Strong immune responses and robust protection following a novel protein in adjuvant tuberculosis vaccine candidate. (PubMed, Sci Rep) - "M72/AS01E, demonstrated 49.7% efficacy in preventing active TB in latently infected adults, indicating that protective immunity through subunit vaccines is possible...Heterologous vaccination strategies were also explored by combining intranasal ChAdOx1.PPE15 viral vector, with intramuscular PPE15-LMQ resulting in improved protection compared to individual vaccines. These findings support the progression of this vaccine candidate to the next stages of development."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4 • CXCR3 • KLRG1

Validation of a 28-color intracellular cytokine staining assay in preparation for the M72/AS01 TB vaccine trial immune correlates study (HIVR4P 2024) - "BACKGROUND: The GSK TB-018 M72/AS01E TB vaccine trial demonstrated 49.7% efficacy in reducing progression to active TB disease in adults with Mycobacterium tuberculosis (M.tb) infection... The newly developed 28-color assay passed the criteria for accuracy, precision and linearity and is fit for purpose for the planned immune correlates studies. The assay includes a range of functional and phenotyping markers to fully characterize TB-specific T-cell responses."

Infectious Disease • Respiratory Diseases • Tuberculosis • CD4 • CD8 • IFNG