MetE: a promising protective antigen for tuberculosis vaccine development.

INTRODUCTION: Tuberculosis (TB), caused by(MTB), remains a significant global health concern. The existing vaccine, Bacillus Calmette-Guérin (BCG), provides inconsistent protection, highlighting the pressing need for a more effective vaccine. We aimed to identify novelantigens and assess their protective efficacy as TB vaccine candidates.

METHODS: Using immunopeptidomics, we identified 64 and 80 unique mycobacterial antigens derived from BCG and MTB, respectively. We prioritised antigens based on HLA allele coverage through an immunoinformatics approach.

RESULTS: The candidates,,, and, delivered as DNA vaccines, were evaluated for efficacy in mice using the ex vivo Mycobacterial Growth Inhibition Assay (MGIA) andwas identified as a promising candidate. In vivo murinechallenge experiments confirmed the protective efficacy conferred bywhen formulated as recombinant protein with AS01™ or AddaS03™ adjuvants, compared to the naïve group. The immunogenic profiles offormulated in the two different adjuvants differed, with-AS01™ inducing antigen-specific IFN-γ, TNF-α, IL-2, IL-17, IgG1 and IgG2a-c, while-AddaS03™ induced TNF-α, IL-2, IL-17, IL-4, IgM, IgG1, IgG2b.

CONCLUSION: Our findings highlightas a promising protective antigen for future TB vaccine development.