Periodic Reporting for period 1 - TBVAC-HORIZON (Improving understanding of lung immunity in tuberculosis to establish a diverse, innovative TB vaccine pipeline targeting mucosal immunity)
Reporting period: 2023-04-01 to 2024-09-30
Tuberculosis (TB) remains one of the most devastating infectious diseases worldwide, killing over 4,000 people every day. Prevention of tuberculosis infection by novel vaccines would provide the most cost-effective approach to end the disease. The only existing licensed vaccine BCG (Bacille Calmette-Guérin) protects children from severe forms of disseminated TB disease, but fails to reliably prevent pulmonary TB in adolescent and adult populations. Improved and novel vaccines are urgently required. Though few promising TB candidate vaccines exist, innovative new platforms and strategies are needed to ensure that the most effective and affordable vaccines are developed and/or improved, and to adequately (re-)fill the pipeline of candidate vaccines.
To this end, TBVAC-HORIZON will - with specific focus on investigations of the immune protection in the lung - innovate and diversify the global TB vaccine pipeline and accelerate the development of novel candidate vaccines. This will be achieved by bottom-up research on composition, spatial organisation and functioning of protective immune responses in the Mtb infected lung (WP1), performing clinical and medicinal studies to evaluate whether mucosal revaccination with BCG and candidate live attenuated vaccines improves protective efficacy (WP2), by the identification of host immune response profiles and biomarkers of natural and vaccine-induced immune protection in the lung (WP3) and by support of next generation TB vaccine development (WP4) through standardised head-to-head vaccine candidate testing in animal models, identification and evaluation of novel antigens, delivery systems and adjuvanted formulations, and by development of a new GMP platform for live attenuated vaccines. Aside from these four scientific workpackages a dedicated workpackage for coordination, management, dissemination and exploitation (WP5) ensures optimal harmonisation and synchronisation of all partners' activities and maintaining the connection and links to external collaborators and entities by profiting from the global network of the Project Coordinator TBVI.
TBVAC-HORIZON builds on the extraordinarily successful, long-standing collaboration in previous EU FP5-, FP6-, FP7 and FP8 (H2020)-funded TB vaccine and biomarker R&D projects. Overall, 19 key partners and global leaders with outstanding expertise in the TB R&D field from Europe are partners in the project consortium. The Consortium's research activities are very strongly interwoven. The generated knowledge will be exploited to develop mucosal strategies for translation towards clinical evaluation and implementation. Europe’s leading role in TB vaccine research and innovation will thus be consolidated.
To this end, TBVAC-HORIZON will - with specific focus on investigations of the immune protection in the lung - innovate and diversify the global TB vaccine pipeline and accelerate the development of novel candidate vaccines. This will be achieved by bottom-up research on composition, spatial organisation and functioning of protective immune responses in the Mtb infected lung (WP1), performing clinical and medicinal studies to evaluate whether mucosal revaccination with BCG and candidate live attenuated vaccines improves protective efficacy (WP2), by the identification of host immune response profiles and biomarkers of natural and vaccine-induced immune protection in the lung (WP3) and by support of next generation TB vaccine development (WP4) through standardised head-to-head vaccine candidate testing in animal models, identification and evaluation of novel antigens, delivery systems and adjuvanted formulations, and by development of a new GMP platform for live attenuated vaccines. Aside from these four scientific workpackages a dedicated workpackage for coordination, management, dissemination and exploitation (WP5) ensures optimal harmonisation and synchronisation of all partners' activities and maintaining the connection and links to external collaborators and entities by profiting from the global network of the Project Coordinator TBVI.
TBVAC-HORIZON builds on the extraordinarily successful, long-standing collaboration in previous EU FP5-, FP6-, FP7 and FP8 (H2020)-funded TB vaccine and biomarker R&D projects. Overall, 19 key partners and global leaders with outstanding expertise in the TB R&D field from Europe are partners in the project consortium. The Consortium's research activities are very strongly interwoven. The generated knowledge will be exploited to develop mucosal strategies for translation towards clinical evaluation and implementation. Europe’s leading role in TB vaccine research and innovation will thus be consolidated.
In the first 18 project months important progress has been achieved in tracking immune cells in the lung of Mtb-infected mice using in vivo imaging methods. In conjunction with immunological studies the knowledge on the influence of the pulmonary microenvironment on T cell responses is increasing. These results inform the design and interpretation of vaccination trials in non-human primates and humans as well as the development of delivery platforms and synthetic adjuvants.
The human clinical trial is underway and the aligned, parallel non-human primate study is about to start. Sample collection for the immunological analyses is underway. Immunological assay protocols have been harmonised and exchanged, so samples can be transferred at the appropriate time for analysis.
The human clinical trial is underway and the aligned, parallel non-human primate study is about to start. Sample collection for the immunological analyses is underway. Immunological assay protocols have been harmonised and exchanged, so samples can be transferred at the appropriate time for analysis.
• Establishment and implementation of an in vivo live imaging microscopy facility and novel insights into T cell interaction with TB-infected cells in the lung
• Centralized measurement of specialist assays ready for use, with the highest possible degree of harmonization and assays performed locally on fresh materials
• First batch of adjuvant formulation of two novel antigens from the Consortium has been completed, with assessment ongoing
• Pre-master seed lot of a recombinant vaccine strain successfully prepared, with optimisation of production ongoing.
• Centralized measurement of specialist assays ready for use, with the highest possible degree of harmonization and assays performed locally on fresh materials
• First batch of adjuvant formulation of two novel antigens from the Consortium has been completed, with assessment ongoing
• Pre-master seed lot of a recombinant vaccine strain successfully prepared, with optimisation of production ongoing.