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

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

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

Enrollment closed • Human Immunodeficiency Virus • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4

MESA-TB: Safety and Immunogenicity of a Mycobacterium Tuberculosis Vaccine M72/AS01E in Participants With Well-controlled HIV (clinicaltrials.gov) - P2; N=400; Recruiting; Sponsor: Bill & Melinda Gates Medical Research Institute; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Human Immunodeficiency Virus • Immunology • Infectious Disease • Respiratory Diseases • Tuberculosis • CD4

Predicted Structural Variability of Mycobacterium tuberculosis PPE18 Protein With Immunological Implications Among Clinical Strains. (PubMed, Front Microbiol) - "Recent advancements in vaccinology have led to the development of the M72/AS01E subunit vaccine, of which the major component is the Mycobacterium tuberculosis (MTB) PPE18 protein...Moreover, we found far more residues in the second domain predicted to be B-cell epitopes compared with the first domain. These results suggest an important functional role of the first domain and a role in immune evasion for the second, which extends our knowledge base of the basic biology of the PPE18 protein and indicates the need for further study into non-traditional immunological responses to TB."

Clinical • Journal • Immunology • Infectious Disease • Respiratory Diseases • Tuberculosis

[VIRTUAL] Phase 2b controlled trial of M72/AS01E Vaccine to prevent Tuberculosis and Prevention of M. tuberculosis infection with H4:IC31 Vaccine or BCG Revaccination. (NAPCON 2020) - No abstract available

P2b data • Infectious 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=400; Active, not recruiting; Sponsor: Bill & Melinda Gates Medical Research Institute; Not yet recruiting ➔ Active, not recruiting; Trial completion date: Apr 2022 ➔ Jul 2022; Trial primary completion date: Apr 2022 ➔ Jul 2022

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Immunology • Infectious Disease • Respiratory Diseases • Tuberculosis

The Systematic Review and Meta-Analysis on the Immunogenicity and Safety of the Tuberculosis Subunit Vaccines M72/AS01 and MVA85A. (PubMed, Front Immunol) - " Five eligible randomized clinical trials (RCTs) were selected for the meta-analysis of M72/AS01E candidate vaccines...The M72/AS01 and MVA85A vaccines are associated with a mild adverse reaction. The meta-analysis on immunogenicity and safety of M72/AS01 and MVA85A vaccines provides useful information for the evaluation of available subunit vaccines in the clinic."

Clinical • Retrospective data • Review • Fatigue • Infectious Disease • Musculoskeletal Pain • Pain • Tuberculosis

MESA-TB: Safety and Immunogenicity of a Mycobacterium Tuberculosis Vaccine M72/AS01E in Participants With Well-controlled HIV (clinicaltrials.gov) - P2; N=400; Not yet recruiting; Sponsor: Bill & Melinda Gates Medical Research Institute

Clinical • New P2 trial • Human Immunodeficiency Virus • Immunology • Infectious Disease • Tuberculosis

The status of tuberculosis vaccine development. (PubMed, Lancet Infect Dis) - "Results from clinical efficacy trials, particularly a completed, phase 2b trial for preventing tuberculosis disease in people infected with Mycobacterium tuberculosis using the adjuvanted protein subunit vaccine M72/AS01E give hope. We review the current status of tuberculosis vaccine candidates and outline the diversified vaccine development that are underway."

Journal • Review • Infectious Disease • Tuberculosis

Homoplastic single nucleotide polymorphisms contributed to phenotypic diversity in Mycobacterium tuberculosis. (PubMed, Sci Rep) - "Among the pe/ppe genes, the homoplastic SNPs were common in a relatively small number of homologous genes, including ppe18, the protein of which is a component of a promising candidate vaccine, M72/AS01E...Our study highlights the potential of homoplastic mutations to produce phenotypic changes. Under selective pressure and during interaction with the host, homoplastic mutations may confer advantages to M. tuberculosis and deserve further characterization."

Journal • Infectious Disease • Tuberculosis