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

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

Momentum of hope: The journey toward a universal TB vaccine. (PubMed, Trop Doct) - "Recent developments, such as the M72/AS01E vaccine, demonstrate promising results in increasing protection against TB in adults with latent infections...The pursuit of more effective TB vaccines, capable of providing broader protection across all age groups, is paramount. This effort not only aligns with the WHO's End TB Strategy but also offers hope for a future where TB is no longer a global health crisis."

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

Study to Assess Efficacy and Safety of M72/AS01E-4 Mycobacterium Tuberculosis (Mtb) Vaccine in Adolescents and Adults (clinicaltrials.gov) - P3 | N=20000 | Recruiting | Sponsor: Bill & Melinda Gates Medical Research Institute | Not yet recruiting ➔ Recruiting | Trial completion date: Aug 2029 ➔ Apr 2028 | Trial primary completion date: Aug 2029 ➔ Apr 2028

Enrollment open • Trial completion date • Trial primary completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Study to Assess Efficacy and Safety of M72/AS01E-4 Mycobacterium Tuberculosis (Mtb) Vaccine in Adolescents and Adults (clinicaltrials.gov) - P3 | N=26000 | Not yet recruiting | Sponsor: Bill & Melinda Gates Medical Research Institute

New P3 trial • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

MESA-TB: Safety and Immunogenicity of a Mycobacterium Tuberculosis Vaccine M72/AS01E in Participants With Well-controlled HIV (clinicaltrials.gov) - P2 | N=402 | Completed | Sponsor: Bill & Melinda Gates Medical Research Institute | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4

The quest for vaccine-induced immune correlates of protection against tuberculosis. (PubMed, Vaccine Insights) - "A statistical framework to integrate the data analysis strategy was developed. Exploratory analyses will be performed to generate novel hypotheses."

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

Potential implementation strategies, acceptability, and feasibility of new and repurposed TB vaccines. (PubMed, PLOS Glob Public Health) - "We identified potential implementation strategies for the M72/AS01E vaccination and BCG-revaccination-like candidates and explored their acceptability and feasibility...Our study provides crucial information for implementing novel TB vaccines in specific target groups and on country specific acceptability and feasibility. Key groups for vaccine implementation in these settings were identified, and should be included in clinical trials and implementation planning."

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

New tuberculosis vaccines in India: Quantifying the potential health and economic impacts of adolescent/adult vaccination with M72/AS01E-like and BCG-revaccination-like vaccines (V-Congress 2022) - No abstract available

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

New tuberculosis vaccines in India: evaluating the potential health impacts of adolescent/adult vaccination with M72/AS01E-like and BCG-revaccination-like vaccines (ECCMID 2022) - No abstract available

Clinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Updating age-specific contact structures to match evolving demography in a dynamic mathematical model of tuberculosis vaccination. (PubMed, PLoS Comput Biol) - "We simulated an M72-AS01E-like tuberculosis vaccine delivered from 2027 and estimated the per cent TB incidence rate reduction (IRR) in 2050 under each update method...We found that model-based TB vaccine impact estimates were relatively insensitive to demography-matched contact matrix updates in an India-like demographic and epidemiologic scenario. Current model-based TB vaccine impact estimates may be reasonably robust to the lack of contact matrix updates, but further research is needed to confirm and generalise this finding."

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