Paulo Bettencourt Poster 2024

Paulo Bettencourt

Asst Prof   Paulo Bettencourt

Catholic University of Portugal    Portugal

Antigen Prioritization for the Development of Tuberculosis Vaccines

Poster Abstract

Rita Ferreira, David Pires, Paulo J.G. Bettencourt

Tuberculosis (TB), the leading cause of death by an infectious disease worldwide, killed 1.3 million people in 2022. Bacillus Calmette-Guerin (BCG) is the only approved vaccine for TB. While BCG is effective in preventing TB meningitis and disseminated disease in children, its efficacy in adolescents and adults is inconsistent and it does not prevent transmission. New vaccines to replace or boost BCG are urgently needed.

Correlates of Protection are not well established for BCG, but protection against TB is strongly dependent on CD4 T-cells and to some extent, CD8 T-cells. To recall BCG-specific T-cells, BCG-specific peptide-ligands presented by MHC-I and MHC-II are required. Immunopeptidomics, is an unbiased method for peptide identification. Recently, 94 mycobacterial peptides presented by MHC-II and 43 presented by MHC-I, were identified in BCG-infected THP-1 cells, with a defined HLA-type, to facilitate the peptide identification. In order to design vaccines that include all putative HLA ligands covering individuals worldwide, full-length antigens were selected, instead of single peptides. Three antigens were expressed in viral vectors and evaluated as vaccine candidates in a murine aerosol Mycobacterium tuberculosis challenge. The antigens Galactofuranosyl transferase (glfT2), Isoniazid inductible gene (iniB) and Probable fatty acid synthase (fas), when delivered as viral vectors to boost previous BCG vaccination, conferred significant protection in the lungs and spleen of mice when administered in combination, compared to BCG alone.

A number of potential vaccine candidates remain to be characterized. Here we evaluated the PBMC responses of BCG-vaccinated individuals, using IFNγ-ELISpot, and propose to rank and prioritize these peptides, using pre-defined and pre-weighted criteria.