TBVI is continuously working on supporting the development of new vaccine candidates. Vaccine developers are kindly invited to share an update if needed by contacting TBVI.
The current TB vaccine pipeline (last update October 2022), is as follows:

Preclinical Phase 1 Phase 2a Phase 2b Phase 3
Infants & neonates

BCG-ZMP1

University Zurich, TBVI

BCG-ZMP1

rBCGΔzmp1 is a recombinant BCG developed by the University of Zürich. Its primary target is global boosting. On the basis of its attenuated profile, it also aims to safely replace BCG in the (HIV-exposed) new-borns. Proof of concept studies on immunogenicity, safety and protective efficacy were performed in mice, guinea pigs and cattle. Further studies are ongoing.

VPM1002

SII, Max Planck, VPM, TBVI

VPM1002

VPM1002 is a live-attenuated, recombinant Bacille Calmette-Guérin vaccine (BCG), originating from the Max Planck Institute for Infection Biology. This new vaccine has been developed in the clinics by the Hannover-based Vakzine Projekt Management GmbH (VPM) through the phase IIa study. VPM has teamed up with Serum Institute of India Pvt. Ltd. (SIIPL) and together they have conducted a phase II trial in South Africa evaluating VPM1002 as a prime vaccine in healthy HIV-exposed and HIV-unexposed infants. The subsequent pivotal phase III trial, funded by SIIPL and European and Development Clinical Trial Partnership (EDCTP), is currently in the preparation phase and is planning to start 2020 ( https://www.prime-vaccine.eu/ ). Newborn infants are the primary target population as the ultimate goal is to replace the current BCG with VPM1002. Data from the first clinical trials have confirmed the pre-clinical data and showed that VPM1002 is at least as safe and immunogenic as BCG. In addition, a phase II/III trial is currently ongoing in India to assess the potential of VPM1002 as a post-exposure vaccine in prevention of TB recurrence after successful anti-tuberculosis drug therapy.

MTBVAC

Biofabri, Unizar, TBVI

MTBVAC in newborns

MTBVAC, developed by the University of Zaragoza, Institut Pasteur and Biofabri, is a live attenuated Mtb strain currently in clinical development. Its primary target population is newborns and secondary adolescences. The safety and immunogenicity results of the Phase I trial conducted at the University of Lausanne as well as the Phase Ib trial in infants within the South African Tuberculosis Vaccine Initiative (SATVI) were supportive to move to the next stage. The clinical Phase IIa in newborns has started in 2019 and is finalised in 2022. The Phase III started Q3 2022.
Adolescents & Adults

H107

SSI, TBVI

H107

H107 is the successor of a combination of H64, H74 and H76 concepts. It is a protein fusion vaccine developed by Statens Serum Institut. H64 consists of six strongly expressed proteins. The fusion protein is highly immunogenic when administered in CAF01, an adjuvant that has recently demonstrated induction of CMI responses in humans. The primary target of the H107 vaccine is to supplement the BCG vaccine. Ongoing experiments within the TBVAC2020 consortium are investigating which epitopes are immunodominant during M.tb infection and if removal of the dominant epitopes will allow for exposure of cryptic/subdominant epitopes and improved protection.

BCG, ChadOx/MVA PPE15-85A

Univ. of Oxford, TBVI

BCG, ChadOx/MVA PPE15-85A

ChAdOx1.PPE15 is a recombinant, replication deficient chimpanzee adenovirus constructed in Oxford, expressing the mycobacterial PPE15 protein. This candidate is part of the overall UOXF TB vaccine programme to work towards a BCG booster vaccination regimen in adolescents and young adults. Four candidate antigens were identified and cloned into the simian adenoviral vector, ChAdOx1. In mouse experiments, ChAdOx1.PPE15 showed the most interesting results to further evaluate. Currently ChAdOx.PPE15, has been evaluated in guinea pigs and conferred superior protection to BCG alone in the spleen. An experiment to evaluate a 5-Ag insert in ChAdOx1 and MVA is now underway in non-human primates.

CMV-6Ag

Aeras, Vir Biotech, OHSU

CysVac2/Ad

University Sydney, TBVI

CysVac2/Ad

CysVac2/Advax is a fusion protein vaccine developed by the The University of Sydney and Vaxine. The vaccine includes proteins designed to target both active and chronic infection with Mycobacterium tuberculosis. Preclinical experiments in mice demonstrate that the fusion protein affords strong protective efficacy against M. tuberculosis infection when combined with the novel polysaccharide adjuvant AdvaxC. AdvaxC has shown a good safety profile and induction of T and B cell responses in previous human vaccine trials. On-going preclinical experiments are examining the ability of the vaccine to protect in additional animal models and how to improve the vaccine in order to strengthen the case for clinical development of the vaccine.

BCG-ZMP1

University Zurich, TBVI

BCG-ZMP1

rBCGΔzmp1 is a recombinant BCG developed by the University of Zürich. Its primary target is global boosting. On the basis of its attenuated profile, it also aims to safely replace BCG in the (HIV-exposed) new-borns. Proof of concept studies on immunogenicity, safety and protective efficacy were performed in mice, guinea pigs and cattle. Further studies are ongoing.

Ad5 Ag85A

McMaster, CanSino

ChadOx1.85A MVA 85A Aerosol / IM

Univ. of Oxford, TBVI

ChadOx1.85A MVA 85A Aerosol / IM

• As part of their TB vaccine programme, University of Oxford is developing an aerosol inhaled TB vaccine regimen. This route of administration of a TB vaccine could offer practical, tolerability and safety benefits over and above needle-based methods. This may be particularly important for developing countries. Three phase I clinical trials with aerosol MVA85A evaluating the safety and immunogenicity of this route of vaccination have been conducted, the first two trials in BCG-vaccinated subjects and the third in M.tb latently infected subjects. A phase I trial with aerosol ChAdOx1.85A, conducted by Prof F Spertini at CHuV, Lausanne, has now completed and will soon be published. Furthermore, ongoing studies with aerosol BCG continue to inform the development of an aerosol TB vaccine.

TB/Flu04L

RIBSP

MTBVAC

Biofabri TBVI UNIZAR IAVI

MTBVAC

MTBVAC, developed by the University of Zaragoza, Institut Pasteur and Biofabri, is a live attenuated Mtb strain currently in clinical development. Its primary target population is newborns and secondary adolescences. The safety and immunogenicity results of the Phase I trial conducted at the University of Lausanne as well as the Phase Ib trial in infants within the South African Tuberculosis Vaccine Initiative (SATVI) were supportive to move to the next stage. The clinical Phase IIa in newborns has started in 2019 and is expected to be finalised in 2020.

ID93/GLA-SE (QTP101)

Quratis

AEC/BC02

Anhui Zhifei Longcom

M72 + ASO1

GSK, GMRI

DAR-901

Dartmouth University, Aeras

H56:IC31

SSI, Valneva, Aeras

BCG Revaccination

Gates MRI

VPM1002

SII, Max Planck, VPM

MIP

Cadila Pharma

GamTBVac

MoH Russia
Therapeutic

MVA Multiphasic vac.

Transgene, TBVI

MVA Multiphasic vac.

Transgene is developing therapeutic candidate vaccine against Mycobacterium tuberculosis. A range of MVA constructs expressing from 6-10 TB antigens covering all 3 phases of the infection (active, latency/dormancy, resuscitation) was generated. One lead MVA candidate expressing 10 antigens was selected in preclinical studies showing its immunogenicity in different mouse strains and its efficacy in two mouse post-exposure models. Transgene aims to bring the MVA lead candidate to the clinic to improve treatment of TB, in particular linked to DR (drug resistant) strains, and to prevent reactivation and/or re-infection in the adult DS (drug sensitive)/DR population, in particular from endemic countries.

H107

SSI

ID93/GLA-SE

ACTG, HVTN

H56:IC31

SSI, Valneva

TB/Flu01L

RIBSP

RUTI Archivel Pharma

RUTI Archivel Pharma

RUTI® is a non-live immunotherapeutic agent based on cell wall fragmented Mycobacterium tuberculosis. RUTI® is intended as a therapeutic vaccine to be used in conjunction with the standard antibiotic treatment. Its target is to improve the cure rate and to reduce the relapse incidence focusing mainly on Multi Drug resistant TB (MDR-TB). A Phase II clinical trial in LTBI adults has been successfully completed. The Phase IIa clinical safety and immunogenicity trial in patients with MDR-TB has finalized and the results are under analysis.

Ruti Archivel Pharma

Ruti Archivel Pharma

A phase 2b trial is being conducted under the STriTuVaD H2020 consortium and DBI India. The efficacy, safety and immunogenicity of RUTI administered at the beginning of the TB antibiotic treatment is being evaluated in adult patients with DS-TB and with MDR-TB.

VPM1002

SII, Max Planck, VPM

  • Live

  • Wholecell

  • Subunit

  • Vector

  • TBVI involved

TBVI provides technical support for product and clinical development to TB vaccine researchers and developers.

TBVI has initiated and coordinated the realisation of a joint publication regarding preferred product characteristics (PPC) for therapeutic vaccines to improve tuberculosis treatment outcomes. This PPC is a result of a consensus generating consultation process from the WHO, TBVI and IAVI with input from experts within the TB field and beyond. To read the full publication, please follow the link: “Preferred product characteristics for therapeutic vaccines to improve tuberculosis treatment outcomes: Key considerations from World Health Organization consultations”.

TB Vaccine development pathway

The TB vaccine pipeline requires a global and comprehensive coordination of efforts with defined stages of development and criteria for progression of individual vaccine candidates. To address this, the TB Vaccine Development Pathway is an established tool that provides a structured development path and gating criteria for TB vaccine candidates. It also describes the different functions and capabilities required to advance a candidate TB vaccine to its next stage of development.

For more information about the Pathway, please visit www.TBVacPathway.org , read the article published in Tuberculosis The TB vaccine development pathway – An innovative approach to accelerating global TB vaccine development and/or Stage Gating Criteria Tables 2021

For more information, please contact Marit Holleman.