MTBVAC / Zendal Group - 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

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

SAFETY, REACTOGENICITY AND IMMUNOGENICITY OF MTBVAC IN NEWBORNS IN A TB ENDEMIC AREA: A PHASE 2A RANDOMIZED, DOUBLE-BLIND, DOSE-DEFINING TRIAL (ESPID 2024) - "Conclusions/Learning Points MTBVAC appeared safe, well tolerated and immunogenic at doses between 2.5×10⁴ CFU and 2.5×106 CFU in South African newborns. The 2.5×105 CFU MTBVAC dose was selected for the ongoing phase 3 trial in a high TB prevalence setting"

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

Susceptibility testing of the live attenuated tuberculosis vaccine BCG and the vaccine candidate MTBVAC to currently WHO-recommended anti-tuberculosis drugs by the EUCAST method. (PubMed, Clin Microbiol Infect) - No abstract available

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

Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection - Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug Resistance. (PubMed, Med Sci Monit) - "MTBVAC is the first live attenuated vaccine to prevent Mycobacterium tuberculosis infection, with phase 2a safety and efficacy clinical trial data expected at the end of 2024. This editorial aims to summarize the current challenges and hopes for developing vaccines to prevent HIV infection and approaches to overcome antiretroviral drug resistance as a cure for HIV/AIDS."

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

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 | Not yet recruiting | Sponsor: International AIDS Vaccine Initiative

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

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 | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4 • CD8

MTBVACN3: Efficacy, Safety and Immunogenicity Evaluation of MTBVAC in Newborns in Sub-Saharan Africa (clinicaltrials.gov) - P3 | N=6960 | Recruiting | Sponsor: Biofabri, S.L | Trial primary completion date: Jun 2027 ➔ Jun 2028

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

HVTN605A5421: Evaluating the Safety and Immunogenicity of MTBVAC in Adolescents and Adults Living With and Without HIV in South Africa (clinicaltrials.gov) - P2a | N=276 | Not yet recruiting | Sponsor: HIV Vaccine Trials Network | Initiation date: Aug 2023 ➔ Jan 2024

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

HVTN605A5421: Evaluating the Safety and Immunogenicity of MTBVAC in Adolescents and Adults Living With and Without HIV in South Africa (clinicaltrials.gov) - P2a | N=276 | Not yet recruiting | Sponsor: HIV Vaccine Trials Network

New P2a trial • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4 • CD8