MIT Identifies TB Vaccine Targets and Supercharges mRNA Antigen Display in Preclinical Study

Overview

• Published in Science Translational Medicine, the study mapped 27 Mycobacterium tuberculosis peptides from 13 proteins presented on human MHC class II, with 24 triggering T cell responses in donor samples.
• The team infected human phagocytes, isolated MHC–peptide complexes from cell surfaces, and used mass spectrometry to empirically define antigens recognized by CD4+ T cells.
• High-priority candidates were enriched for type 7 secretion system proteins, notably EsxA, EsxB and EsxG, which are involved in bacterial escape from phagocyte compartments.
• Prototype mRNA constructs encoding EsxB and EsxG targeted to lysosomes drove roughly 1,000-fold higher presentation of TB peptides, and adding EsxA further increased display consistent with its role in forming functional complexes.
• The researchers assembled an eight-protein vaccine candidate to broaden coverage across diverse MHC variants and are testing it with global donor blood samples ahead of planned animal studies, with human trials several years away.