TBVI is continuously working on the development of new vaccine candidates.
The current TB vaccine pipeline (last update January 2017), is as follows:

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


TBVI consortium vaccine candidates

Preclinical candidates

Combination vaccines (prime-boost), GSK
New preclinical candidate vaccines have been developed at GSK and tested in a preclinical experiment. These new candidates consist of different combinations of the ChAd3M72 and M72/AS01E. The preclinical experiments have shown promising immunological results. The aim is to further develop a candidate for prime-boost or co-administration strategies.

rBCGΔais1/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.

H64 + CAF01
H64 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 H64 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.

Therapeutic vaccine-MVA platform, Trangene SA
Transgene is evaluating the MVA platform for developing therapeutic candidate vaccines against Mycobacterium tuberculosis. Transgene has generated a range of MVA constructs expressing from 6-10 TB antigens covering all 3 phases of the infection (active, latency/dormancy, resuscitation). Preclinical studies have shown that those MVA constructs have promising immunological results. Transgene aims to bring one selected MVA 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) population, in particular from endemic countries.

ChAdOxPPE15, UOXF
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, is being evaluated in guinea pigs to test whether protective efficacy of BCG can be improved in this more stringent model.

CysVac2, UNISYD
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 (e.g guinea pigs) and define efficacy in post-exposure models, in order to strengthen the case for clinical development of the vaccine.

 

Clinical candidates

Aerosolised MVA85A
As part of their TB vaccine programme, University of Oxford is developing an aerosol inhaled route of TB vaccine delivery. 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. A second clinical trial phase I with aerosol MVA85A has just completed in Oxford, to further evaluate the effect of this route of immunisation on anti-vector immunity, and a third clinical trial evaluating safety of aerosol MVA85A in latently-infected healthy UK adults has just started enrolment.

MTBVAC
MTBVAC, developed by the University of Zaragoza, Institut Pasteur and Biofabri, is a live attenuated Mtb strain currently in early 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 were satisfactory. In September 2015, MTBVAC has move forward to a Phase Ib trial in infants within the South African Tuberculosis Vaccine Initiative (SATVI). Results of this trial are expected in Q4 2017.

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 are currently conducting a phase II trial in South Africa evaluating VPM1002 as a prime vaccine in HIV-exposed and HIV-unexposed infants. This will also be 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 III trial will start in India to assess the potential of VPM1002 as a post-exposure vaccine in prevention of TB recurrence after successful anti-tuberculosis drug therapy.

RUTI
Description coming soon

 

 

For more information, please contact Daniëlle Roordink.