FIGHT_TB: FIndinG High-grade anTigens towards an innovative TB vaccines

Tuberculosis (TB) poses a serious threat to global human and animal public health. Indeed, TB is still one of the most important infective diseases that causes more than 1 million victims every year due to the lack of efficient drug treatments and prevention. As a result of the coronavirus disease 2019 (COVID-19) pandemic, the global TB mortality rate in 2020 has further raised up, making TB prevention and control even more challenging. Vaccination has been considered the best approach to reduce the TB burden. Since 1923, the Bacillus Calmette–Guérin (BCG) vaccine, an attenuated form of Mycobacterium bovis, remains the only licensed vaccine and has poor efficacy. Therefore, it is urgent to develop new TB vaccines aimed either to replace or boost BCG. Subunit vaccines, containing purified parts of the pathogen, are highly promising since they can overcome safety concerns and optimize antigen targeting. Nevertheless, these vaccines need to be engineered to enhance their immunogenicity, decrease the needed antigen dose and ensure a targeted delivery and interaction with the immune cells. Structural insights of key molecular players in TB are fundamental for a deeper understanding of host-pathogen interaction and for the exploration of novel approaches in vaccine development. Based on an established collaboration with immunologists at Chungnam National Univerisy College of Medicine (South Korea), this project is based on structural vaccinology approach for the identification and the characterization of promising antigenic candidates for the design of new improved antigenic molecules. In this framework, the PRIN 2022 PNRR- FIGHT_TB team (IBB and UNISA), working for the last 10 years on potential drug targets and vaccine antigen candidates as novel therapeutic options, combine different skills and methodologies in a rational way for the development of an innovative multi-antigenic molecules against TB.