Service(s) working on this project
Sciensano's project investigator(s):
Tuberculosis (TB) is caused by infection with bacteria of the Mycobacterium tuberculosis complex, spread by individuals suffering pulmonary tuberculosis. It is still among the top 10 causes of death worldwide, with 1.6 million deaths and 10.0 million new cases in 2017. The treatment success rate of tuberculosis is 83%. However, it falls to 52% in the case of Multi-Drug-Resistant tuberculosis. The Bacille Calmette-Guérin (BCG) vaccine is still currently the only vaccine administered at birth for TB prevention in endemic countries and confers a highly variable protection against pulmonary TB in adults (ranging from 0% to 80%).
Several vaccine candidates have been developed in the last 3 decades and fall in 2 categories:
- live attenuated vaccines to replace BCG,
- sub-unit vaccines to be administered as booster vaccines in adulthood.
Although some of these have reached clinical evaluation, their improved efficacy is not guaranteed and the design of vaccine candidates should continue in order to achieve the development of a new generation and efficient TB vaccine.
This collaborative project aims to further investigate the vaccine potential of different novel live-attenuated and subunit vaccine candidates in development by the partners of this proposal in the pre-clinical mouse and rat models of Mtb infection.
In this project, 2 teams from the Institut Pasteur of Paris, 1 team from Sciensano, 1 team from the University of Pisa and 1 team from the Institute of Pharmacology and Structural Biology of Toulouse associate their complementary expertise (immunology, vaccinology, tuberculosis and lentiviral vectors) in order to contribute to the development of better preventive and therapeutic approaches against human Tuberculosis.
More specifically, vaccine potential of lentiviral vectors encoding multiple antigens of Mycobacterium tuberculosis to be used in preventive and therapeutic approaches are designed and investigated, using preclinical models. Lentiviral vectors are gene transfer vectors derived from HIV, which are strictly non-replicative since they are deleted of all HIV coding sequences, but express genes of interest, such as genes of selected Mycobacterium tuberculosis antigens in this project. The administration of lentiviral vectors based vaccines induces intense and long-lasting cellular immune responses specific to the expressed antigens.
These lentiviral vectors vaccines will be tested as booster vaccines in combination with live-attenuated priming vaccine candidates in development as vaccines to replace BCG or will be tested in therapeutic approaches.
This project will generate data which will contribute to the development of next preventive and therapeutic approaches for tuberculosis.