TBVAC2020 obtained the following substantial results:
WP1. WP1 identified 12 new approaches for novel vaccines (including 4 whole-cell and 6 subunit vaccines) with higher efficacy than BCG in TB challenge models. These were forwarded into advanced animal models and will deliver new vaccines for clinical trials. Considerable progress has also been achieved in the delivery of antigens using new vectors (e.g. HIV- and LCMV-derived), delivery systems (nanoparticles and liposomes), routes of delivery and adjuvants (cell-stimulating compounds, lipoproteins, glycolipids and polysaccharides) that strengthen the development of local immunity in the lung.
WP2. A number of novel preclinical models have been developed, each with a specific clinical objective. The preclinical toolbox has been diversified by models that recapitulate vaccine performance after post-exposure/therapeutic vaccination for prevention of relapse, vaccination in the context of TB risk factors, by refining existing models for enhanced readout through implementation of assays for the analysis of T lymphocyte function in guinea pigs, PET-CT imaging to monitor host inflammation and disease dynamics in non-human primates.
New leads for antigenic vaccine targets, signatures of functional T lymphocyte activation and exhaustion that correlate with risk of disease, and signatures of local polyfunctional Th17, IL10 and antigen-specific antibodies as correlates of protective immunity upon pulmonary mucosal vaccination have been identified.
WP3. In WP3 head-to-head testing of vaccines to date has provided safety, immunogenicity and efficacy data on 44 different vaccine concepts and formulations (including e.g. new routes of administration or new technologies) selected from a total of 64 applications for testing. These data enabled decisions on progression of vaccines from early discovery stages to pre-clinical development or iterative improvements in vaccine design. Altogether 13 vaccines were demonstrated to provide protection against M. tuberculosis (Mtb) challenge of which 7 were significantly better than BCG. Five vaccine candidates were selected for preclinical development.
WP4. A viral vector candidate has been selected for an experimental medicine study in humans to evaluate safety and local mucosal immunogenicity after administration via the aerosol route. The study after approval by regulatory authorities started in late 2018. Dose finding tests have been completed. No safety signals have been noticed in the vaccinated volunteers, and no vaccine related serious adverse event observed. Last patient follow-up visit is scheduled for early summer 2020.
WP5. WP5 identified, tested, evaluated and prioritized surrogate-endpoints of protection in human TB. Correlates were evaluated in carefully characterised, complementary and unique human cohorts from genetically and geographically diverse populations. Selected correlates were forwarded towards developing, harmonizing and standardizing correlate tests. Efforts are underway to develop these further into simple point-of-care tests for use in high burden and often lower resourced areas. WP5 also studied correlates of risk for TB disease in the above-mentioned cohorts. These will be extremely useful in stratifying individuals in observational and clinical intervention studies. To support data mining of genome wide host expression data a TB biomarker database has been developed containing 51 studies describing transcriptome signatures in patients with active TB disease. It contains not only published signatures but also all genes that are significantly differentially expressed between TB patients and appropriate control populations and will become public domain.
WP6. The PMC did review all candidates submitted to be evaluated in preclinical head-to-head models, and in clinical studies (overall 64 for head-to-head tests, and 4 for clinical testing). Its members participated in the continuous update of the stage gating criteria for progressing TB vaccine candidates along the development pipeline. Specific product and clinical development teams composed of experts in product and clinical development have supported further development of 8 candidate vaccines in preclinical or clinical development stages.
WP7. The annual TBVAC2020 meetings in 2018 and 2019 took place in Les Diablerets, Switzerland, and were preceded by public symposia covering progress issues in TB biomarker & vaccine R&D. The meetings were attended by up to 170 participants from 18 countries, representing research institutes, pharma, SMEs, funding and policy agencies, and partner organisations.
