To Clinical Evaluation of MTBVAC: A New Attenuated Tuberculosis Vaccine Based on phoP Inactivation
Event details
| Date | 06.02.2012 |
| Hour | 13:00 |
| Speaker | Prof Carlos Martin |
| Location | |
| Category | Conferences - Seminars |
PhoP is essential for intricate virulence networks in M. tuberculosis. The inactivation of phoP gene in M. tuberculosis leads to high attenuation in cellular and animal models. The M. tuberculosis phoP mutant, SO2, is more attenuated than M. bovis BCG Pasteur in immunocompromised SCID mice by aerosol and intravenous routes and protected guinea pigs and non-human primates against tuberculosis infection. A key aspect of the variable efficacy conferred by BCG may be insufficient induction of long-lived memory T-cell responses. When compared to M. tuberculosis, M. bovis has deleted many regions of its genome. In addition, during the attenuation process of BCG, additional genes were lost, leading to loss of either virulence factors or additional immunodominant antigens. Recent work published by J. Triccas provides data on the mechanism for the increased protection afforded by M. tuberculosis phoP-based vaccines. SO2 Vaccination results in higher expansion and differentiation of antigen-specific CD4+ T cells into effector and memory T cells compared to BCG in vaccinated mice. Memory T cells were more capable of differentiation into functional effector cells upon challenge with M. tuberculosis. In order to develop a safe and more effective vaccine that could replace BCG, we have constructed a new live vaccine, designated MTBVAC, through the rational attenuation of a M. tuberculosis clinical isolate. MTBVAC is based on two stable independent deletions of two virulence genes, phoP and fadD26; deletion of fadD26 eliminates DIM synthesis, a family of lipids linked with M. tuberculosis virulence. MTBVAC is the first live attenuated candidate vaccine fulfilling the Geneva consensus requirements for live mycobacterial vaccines. Manufacturer and industrial partner BIOFABRI has finalised a Good Manufacturing Practices grade production process for freeze dried MTBVAC live vaccine, and is ready for clinical trials. Final product MTBVAC has demonstrated attenuation, safety and protective efficacy in rigorous non-clinical studies, in agreement with regulatory requirements. Our plan is to progress the live attenuated MTBVAC vaccine candidate to first-in-human clinical evaluation as part of the of TuBerculosis Vaccine Initiative (TBVI).
Links
Practical information
- General public
- Free
Organizer
- Prof. Stewart Cole
Contact
- Prof. Stewart Cole