Journal Article

MetE: a promising protective antigen for tuberculosis vaccine development

Stylianou, Elena, De Voss, Christopher J., Almujri, Salem Salman, Bettencourt, Paulo J. G., Ternette, Nicola, Korompis, Marcellus, Polo Peralta Alvarez, Marco, Nicastri, Annalisa, Li, Shuailin, Satti, Iman, Tanner, Rachel, McShane, Helen

2025

Overview

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 novel antigens and assess their protective efficacy as TB vaccine candidates. 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. The candidates, , , and , delivered as DNA vaccines, were evaluated for efficacy in mice using the ex vivo Mycobacterial Growth Inhibition Assay (MGIA) and was identified as a promising candidate. In vivo murine challenge experiments confirmed the protective efficacy conferred by when formulated as recombinant protein with AS01™ or AddaS03™ adjuvants, compared to the naïve group. The immunogenic profiles of formulated 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. Our findings highlight as a promising protective antigen for future TB vaccine development.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Adjuvants / Adjuvants, Immunologic / Amino acids / Animals / Antibodies / Antigen discovery / Antigens / Antigens, Bacterial - genetics / Antigens, Bacterial - immunology / Bacillus Calmette-Guerin vaccine / BCG / Cytokines - metabolism / DNA vaccines / Experiments / Female / HLA/MHC / Humans / Identification / Immune response / Immunity (Disease) / Immunogenicity / Immunoglobulin G / Immunoglobulin M / Immunoinformatics / Immunology / Immunopeptidomics / Infections / Interleukin 17 / Interleukin 2 / Lymphocytes / Mass spectrometry / Mice / Mycobacterium tuberculosis / Mycobacterium tuberculosis - immunology / Peptides / Protective antigen / Public health / Scientific imaging / Tuberculosis / Tuberculosis - immunology / Tuberculosis - prevention & control / Tuberculosis Vaccines - immunology / Tumor necrosis factor-α / Vaccine Development / Vaccines / Vaccines, DNA - immunology / γ-Interferon