MTBVAC / Zendal Group - 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

A Study to Evaluate the Efficacy, Safety and Immunogenicity of MTBVAC in Adolescents and Adults Living in a TB Endemic Region. (clinicaltrials.gov) - P2 | N=5500 | Active, not recruiting | Sponsor: International AIDS Vaccine Initiative | Recruiting ➔ Active, not recruiting

Enrollment closed • 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

MTBVACph2: Safety and Immunogenicity of a Mycobacterium Tuberculosis Vaccine MTBVAC in Healthy Indian Adults and Adolescents (BBV169/2024) (clinicaltrials.gov) - P2 | N=164 | Active, not recruiting | Sponsor: Bharat Biotech International Limited | Recruiting ➔ Active, not recruiting | Trial primary completion date: Apr 2026 ➔ Sep 2025

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

MTBVAC TB vaccine candidate (ESCMID Global 2026) - No abstract available

HVTN605A5421: Evaluating the Safety and Immunogenicity of MTBVAC (clinicaltrials.gov) - P2 | N=276 | Recruiting | Sponsor: HIV Vaccine Trials Network | Trial completion date: Feb 2026 ➔ Apr 2027 | Trial primary completion date: Feb 2026 ➔ Apr 2027

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

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

A Study to Evaluate the Efficacy, Safety and Immunogenicity of MTBVAC in IGRA Positive Adolescents and Adults Living in a TB Endemic Region. (clinicaltrials.gov) - P2 | N=4300 | Recruiting | Sponsor: International AIDS Vaccine Initiative | Not yet recruiting ➔ Recruiting

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

MTBVACph2: Safety and Immunogenicity of a Mycobacterium Tuberculosis Vaccine MTBVAC in Healthy Indian Adults and Adolescents (BBV169/2024) (clinicaltrials.gov) - P2 | N=164 | Recruiting | Sponsor: Bharat Biotech International Limited

New P2 trial • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

BBV169/2023: Tuberculosis Vaccine in Healthy Indian Adults (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Bharat Biotech International Limited | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

MTBVAC-03: Dose-Defining Safety and Immunogenicity Study of MTBVAC in South African Neonates (clinicaltrials.gov) - P2 | N=99 | Completed | Sponsor: Biofabri, S.L | Phase classification: P2a ➔ P2

Phase classification • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Diagnostic dilemmas and strain diversity in the MTBVAC phase 1b-2a trial in adults. (PubMed, Lancet Glob Health) - No abstract available

Journal • P1/2 data

Live-attenuated Mycobacterium tuberculosis vaccine, MTBVAC, in adults with or without M tuberculosis sensitisation: a single-centre, phase 1b-2a, double-blind, dose-escalation, randomised controlled trial. (PubMed, Lancet Glob Health) - P1b/2a | "MTBVAC at the 5 × 105 dose showed similar safety and reactogenicity and greater immunogenicity when compared to BCG. These results suggest that the 5 × 105 dose of MTBVAC could be selected for a subsequent efficacy evaluation."

Journal • P1/2 data • Dermatology • Human Immunodeficiency Virus • Infectious Disease • Pain • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4

Cytolytic γδ T-cells and IFNγ-producing CD4-lymphocytes characterise the early response to MTBVAC tuberculosis vaccine. (PubMed, NPJ Vaccines) - "Importantly, MTBVAC-activated γδ T-cells had a unique cytotoxic CD16+GZMB+ phenotype, reminiscent of effector cells found in Mtb positive individuals controlling infection. IFN-γ and TNF-α were released in cultures, while IL-17A/F were almost undetectable."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4 • GZMB • IFNG • IL17A • TNFA

Safety, reactogenicity, and immunogenicity of MTBVAC in infants: a phase 2a randomised, double-blind, dose-defining trial in a TB endemic setting. (PubMed, EBioMedicine) - "MTBVAC appeared safe, well-tolerated, and immunogenic at doses between 2.5 × 104 and 2.5 × 106 CFU in South African infants. The 2.5 × 105 CFU MTBVAC dose, being less reactogenic and more immunogenic than BCG, was selected for a multi-centre, phase 3 trial."

Journal • P2a data • CNS Disorders • Dermatology • Human Immunodeficiency Virus • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4 • IFNG

MTBVACN3: Efficacy, Safety and Immunogenicity Evaluation of MTBVAC in Newborns in Sub-Saharan Africa (clinicaltrials.gov) - P3 | N=7120 | Recruiting | Sponsor: Biofabri, S.L | Trial completion date: Sep 2029 ➔ Feb 2029 | Trial primary completion date: Jun 2028 ➔ Feb 2029

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4 • CD8 • IFNG • IL17A • IL2 • IL22

MTBVAC induces superior antibody titers and IgG avidity compared to BCG vaccination in non-human primates. (PubMed, NPJ Vaccines) - "MTBVAC vaccination induced higher titers of IgG, IgM and IgA, and higher avidity IgG compared with BCG vaccination. IgG avidity correlated with protection following M.tb challenge in the same animals, validating the association previously reported between this measure and protection in the context of intravenous BCG vaccination, suggesting that IgG avidity may represent a relevant marker or correlate of protection from TB."

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

Clinical Development of MTBVAC, a live attenuated MTb vaccine (WVCE 2024) - No abstract available

Clinical

Correlation between systemic allergen desensitisation and long-term asthma protection in mice following intravenous administration of the live tuberculosis vaccine MTBVAC. (PubMed, EBioMedicine) - "Altogether, our results suggest that intravenous MTBVAC could be a plausible allergen desensitising approach for treatment of asthma, and could provide long-term protection against allergen exposure."

Journal • Preclinical • Asthma • Eosinophilia • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • IL4 • IL5

HVTN605A5421: Evaluating the Safety and Immunogenicity of MTBVAC in Adolescents and Adults Living With and Without HIV in South Africa (clinicaltrials.gov) - P2 | N=276 | Recruiting | Sponsor: HIV Vaccine Trials Network | Trial completion date: Nov 2024 ➔ Feb 2026 | Trial primary completion date: Nov 2024 ➔ Feb 2026

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4 • CD8

BBV169/2023: Tuberculosis Vaccine in Healthy Indian Adults (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Bharat Biotech International Limited

New P1 trial • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Low-dose M.tb infection but not BCG or MTBVAC vaccination enhances heterologous antibody titres in non-human primates. (PubMed, Front Immunol) - "Our findings suggest that it is unlikely that heterologous antibodies contribute to the non-specific effects of these vaccines. The apparent dysregulation of B cell responses associated with TB disease warrants further investigation, with potential implications for risk of B cell cancers and novel therapeutic strategies."

Journal • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Infectious Disease • Novel Coronavirus Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • Tetanus • Tuberculosis