ORIGINAL RESEARCH article

Front. Immunol.

Sec. Vaccines and Molecular Therapeutics

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1593263

MetE: A Promising Protective Antigen for Tuberculosis Vaccine Development

Provisionally accepted
Salem Salman AlmujriSalem Salman Almujri1*Elena StylianouElena Stylianou2Annalisa NicastriAnnalisa Nicastri3Iman SattiIman Satti2Marcellus KorompisMarcellus Korompis2Shuailin LiShuailin Li2Christopher De VossChristopher De Voss2Marco Polo Peralta AlvarezMarco Polo Peralta Alvarez2Rachel TannerRachel Tanner4Paulo J.G. BettencourtPaulo J.G. Bettencourt5Nicola TernetteNicola Ternette2Helen McShaneHelen McShane2*
  • 1Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
  • 2Jenner Institute, Nuffield Department of Medicine, Medical Sciences Division, University of Oxford, Oxford, England, United Kingdom
  • 3Institute of Cancer Research (ICR), London, England, United Kingdom
  • 4Department of Biology, Mathematical, Physical and Life Sciences Division, University of Oxford, Oxford, England, United Kingdom
  • 5Católica Biomedical Research Centre, Faculty of Medicine, Catholic University of Portugal, Oeiras, Portugal

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (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 MTB 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, hisD, metE, and mmpL12, delivered as DNA vaccines, were evaluated for efficacy in mice using the ex vivo Mycobacterial Growth Inhibition Assay (MGIA) and metE was identified as a promising candidate. In vivo murine MTB challenge experiments confirmed the protective efficacy conferred by metE when formulated as recombinant protein with AS01™ or AddaS03™ adjuvants, compared to the naïve group. The immunogenic profiles of metE formulated in the two different adjuvants differed, with metE-AS01™ inducing antigen-specific IFN-

Keywords: Tuberculosis, Mycobacteirum tuberculosis, Vaccines, immunopeptidomics, immunoinformatics, Antigen discovery, HLA/MHC

Received: 13 Mar 2025; Accepted: 26 Jun 2025.

Copyright: © 2025 Almujri, Stylianou, Nicastri, Satti, Korompis, Li, De Voss, Peralta Alvarez, Tanner, Bettencourt, Ternette and McShane. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Salem Salman Almujri, Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
Helen McShane, Jenner Institute, Nuffield Department of Medicine, Medical Sciences Division, University of Oxford, Oxford, OX3 7DQ, England, United Kingdom

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material